Should kidney allografts from old donors be allocated only to old recipients?

In several deceased donor kidney allocation systems, organs from elderly donors are allocated primarily to elderly recipients. The Eurotransplant Senior Program (ESP) was implemented in 1999, and since then, especially in Europe, the use of organs from elderly donors has steadily increased. The proportion of ≥60-year-old donors reported to the Collaborative Transplant Study (CTS) by European centers has doubled, from 21% in 2000-2001 to 42% in 2016-2017. Therefore, in the era of organ shortage it is a matter of debate whether kidney organs from elderly donors should only be allocated to elderly recipients or whether <65-year-old recipients can also benefit from these generally as "marginal" categorized organs. To discuss this issue, a European Consensus Meeting was organized by the CTS on April 12, 2018, in Heidelberg, in which 36 experts participated. Based on available evidence, it was unanimously concluded that kidney organs from 65- to 74-year-old donors can also be allocated to 55- to 64-year-old recipients, especially if these organs are from donors with no history of hypertension, no increased creatinine, no cerebrovascular death, and no other reasons for defining a marginal donor, such as diabetes or cancer.

Severe bleeding complications and multiple kidney transplants in a patient with tuberous sclerosis complex caused by a novel TSC2 missense variant.

We presented an extremely severe case of tuberous sclerosis complex (TSC) in a female patient with recurring, life-threatening bleeding complications related to renal angiomyolipomas. Massive intratumoral hemorrhage required surgical removal of both angiomyolipomatous kidneys and kidney transplantation. During the follow-up period, the patient developed severe metrorrhagia that eventually led to hysterectomy and salpingo-oophorectomy. Bleeding from the operative sites caused the loss of the first kidney transplant received from the mother, and immediate hemorrhagic shock led to the loss of the second, cadaveric kidney allograft. The third kidney transplant had a successful outcome. Pathological analysis of all tissue specimens showed TSC-associated lesions and deformed blood vessels in the surgically removed organs. Molecular genetic analysis of TSC1 and TSC2 in the DNA of peripheral leukocytes identified a novel TSC2 c.3599G>C (p.R1200P) variant. Functional assessment confirmed the likely pathogenicity of the TSC2 c.3599G>C (p.R1200P) variant. To the best of our knowledge, this is the first report of the c.3599G>C (p.R1200P) variant in exon 29 of the TSC2 gene related to a severe clinical course and multiple kidney transplants in a patient with TSC.

Peritoneal Dialysis Catheter Placement Using an Ultrasound-Guided Transversus Abdominis Plane Block.

BACKGROUND: Peritoneal dialysis (PD) catheter placement is usually performed using general or local anesthesia. We present our PD catheter placement experience using an ultrasound-guided transversus abdominis plane (TAP) block, which is a regional anesthesia technique. METHODS: In this study, we analyzed 33 patients from our center with ESRD who underwent PD catheter placement using a TAP block between June 2011 and April 2014. RESULTS: The TAP block was successful for 29/33 (87.9%) patients. Four patients (12.1%) had pain at the incision site and required general anesthesia. There were no anesthesia-, surgery- or catheter-related complications. CONCLUSION: ESRD patients have a substantial number of comorbidities that can be negatively influenced by general anesthesia. Because regional anesthesia has no systemic effect, this procedure could be recommended for this group of patients. A TAP block is an effective, safe method and can be used as the principal anesthesia technique for PD catheter placement.

Development of the Croatian model of organ donation and transplantation.

During the past ten years, the efforts to improve and organize the national transplantation system in Croatia have resulted in a steadily growing donor rate, which reached its highest level in 2011, with 33.6 utilized donors per million population (p.m.p.). Nowadays, Croatia is one of the leading countries in the world according to deceased donation and transplantation rates. Between 2008 and 2011, the waiting list for kidney transplantation decreased by 37.2% (from 430 to 270 persons waiting for a transplant) and the median waiting time decreased from 46 to 24 months. The Croatian model has been internationally recognized as successful and there are plans for its implementation in other countries. We analyzed the key factors that contributed to the development of this successful model for organ donation and transplantation. These are primarily the appointment of hospital and national transplant coordinators, implementation of a new financial model with donor hospital reimbursement, public awareness campaign, international cooperation, adoption of new legislation, and implementation of a donor quality assurance program. The selection of key factors is based on the authors' opinions; we are open for further discussion and propose systematic research into the issue.

[The role of core decompression for the treatment of femoral head avascular necrosis in renal transplant recipients]. / Lijecenje asepticne nekroze glavice femura u bolesnika s bubreznim transplantatom metodom dekompresije.

Avascular bone necrosis is a relatively rare but significant complication in renal transplant recipients because it causes progressive pain and invalidity. It can be the consequence of the action of numerous causative factors, but it is mostly connected to corticosteroid treatment.The underlying pathophysiologic mechanism is a diminished blood flow to the bone leading to necrosis and bone destruction. During the past 25-years period, 570 renal transplantations and five combined kidney and pancreas transplantations were performed in our centre. A part of the patients was lost to follow-up due to the separation of Croatia from the former Republic of Yugoslavia. After transplantation, we revealed aseptic necrosis of the femoral head in five female patients. All patients had a history of treatment with pulse doses of corticosteroids. At transplantation the average age of the patients was 52.2 yrs (range 46 to 62 yrs), and dialytic treatment before transplantation lasted in average 9.2 yrs (range 2.5 to 21.2 yrs). The period between renal transplantation and the development of clinical signs of avascular bone necrosis lasted in average 1.2 yrs (range 0.3 to 2.3 yrs). We will demonstrate our 62-year old female patient with terminal renal failure caused by post-streptococcal glomerulonephritis, who was treated with peritoneal dialysis 2.5 years before renal transplantation. Twenty months before renal transplantation the patient received pulse doses of corticosteroids, together with immunoglobulins and plasmapheresis, for the treatment of an acute polyradiculoneuritis Guillaine Barré. After transplantation a standard immunosuppressive protocol was applied which included tacrolimus, mycophenolate mofetil, corticosteroids and induction with basiliximab. Four months after transplantation the patient started to feel pain in the right hip after longer standing, in addition to the earlier long-lasting problems caused by bilateral coxarthrosis. The pelvic radiograph showed subchondral radiolucencies in the lateral part of the head circumference spreading into the proximal part of the neck of the right femur, which indicated the presence of aseptic necrosis, but these changes could have also been caused by coxarthrosis. Unexpectedly, magnetic resonance imaging (MRI) did not reveal changes characteristic for avascular bone necrosis. Due to the progressively worsening of pain and the radiographic finding, the patient was submitted to decompression surgery of the femoral head. The surgical procedure was performed under diascopic guidance (C-arm) which allowed the correct positioning of a Kuerschner wire. A cannulated drill (diameter 4.0 mm) was placed over the wire and we performed two drillings of the spongiosis of the femoral head through to the subchondral area. Postoperatively, the patient was soon verticalized and advised to walk with crooks during a period of six weeks. This time is necessary to allow the mineralisation and strengthening of the bone which is now better vascularised. The patient recovered well and had no more pain. In renal transplant recipients it is most important to raise suspicion and verify the presence of avascular bone necrosis early, because timely bone decompression surgery can eliminate pain and cure the patient or it can prevent or delay bone destruction. When clinical signs of avascular bone necrosis arise and radiographic or standard MRI findings are negative, additional investigations (i.e. SPECT or MRI with contrast) should be performed to confirm or exclude the diagnosis. In latter phases of the disease, surgical decompression of the femoral head cannot lead to permanent amelioration, and it is inevitable to perform more invasive surgical procedures like "resurfacing" or bone grafting in younger patients, or the implantation of total hip endoprotheses.

[Metabolic disorders in renal transplant recipients]. / Metabolicke komplikacije u primatelja bubreznog presatka.

INTRODUCTION: Advancements in immunosuppressive treatment of renal transplant recipients have significantly increased the graft and patient survival and significantly lowered the incidence of rejection crises. Efforts to increase long term patient and graft survival are directed to the prevention and treatment of cardiovascular diseases because they are the leading cause of mortality in these patients. Traditional risk factors for the development of cardiovascular diseases (e.g., arterial hypertension, posttransplant diabetes mellitus and metabolic lipid disorder) are up to fifty times more frequent among renal transplant recipients than in the general population. The goal of this study was to analyze the prevalence of the above mentioned metabolic disorders in renal transplant recipients, to analyze the impact of immunosuppressive therapy on the manifestation of these mentioned metabolic disorders, and to analyze the antihypertensive therapy applied. SUBJECTS AND METHODS: We analyzed 53 patients that underwent renal transplantation at Rijeka University Hospital Center during a two-year follow-up. Glomerulonephritis was the primary kidney disease in 14 (29.6%), polycystic kidney disease in 10 (18.87%), interstitial nephritis in 7 (13.21%), nephroangiosclerosis in 5 (18.5%), diabetic nephropathy in 4 (7.55%) and other diseases in 13 (24.53%) patients. RESULTS: The study included 53 patients (58.5% male), mean age 49.8 +/- 11.3 (range 27-72) years and mean dialysis treatment before transplantation 56.0 +/- 41.9 months. All patients received triple immunosuppressive therapy including a calcineurin inhibitor/MMF/corticosteroids and induction with IL-2 receptor blocker (daclizumab or basiliximab). Thirty-three (62%) patients were treated with tacrolimus and 20 (38%) with cyclosporine. The mean creatinine value was 144.92 +/- 46.49. Eighteen (34%) patients had creatinine lower than 120 mmol/L and 35 (66%) patients had a level higher than 120 mmol/L. After transplantation, 49 (92.5%) patients were treated for arterial hypertension (arterial hypertension was defined as systolic blood pressure greater than 140 mm Hg and diastolic pressure greater than 90 mm Hg or the routine use of antihypertensive therapy). Patients receiving cyclosporine had a significantly higher incidence of arterial hypertension as compared with patients on tacrolimus (P=0.025). Among patients with serum creatinine level higher than 120 mmol/L, 32 (65.3%) patients had hypertension, 9 (17%) achieved target blood pressure (<130/80 mm Hg), 8 (16.32%) were treated with one drug, 24 (48.98%) with two drugs, 15 (30.61%) with three drugs and 2 (4.09%) with more than three antihypertensives. Only four patients did not take any antihypertensive medication. The most often used antihypertensive drugs were calcium channel blockers (40.4% of patients), beta-blockers (26.6%), and RAS inhibitors (9.2% of patients received ACE inhibitors and 16.5% ARB). In 6 (11.3%) patients, posttransplant diabetes mellitus developed and 21 (39.62%) patients were treated for metabolic lipid disorder. CONCLUSION: In order to identify patients at a higher risk of developing cardiovascular disease with time, it is essential that kidney transplant recipients undergo regular follow up of graft function, blood pressure, and metabolic parameters. Good graft function is important to improve the quality of life and decrease mortality of renal transplant recipients.

Kidney Transplants from Elderly Donors: The Experience of a Reference Center in Croatia.

OBJECTIVES: Our country Croatia is among the global leaders regarding deceased donation rates, yet we are facing organ shortage and concurrently a sharp decline in our acceptance rates for kidney offers. To reevaluate our organ acceptance policy, we retrospectively analyzed the factors that influenced the posttransplant outcomes of kidneys from elderly deceased donors at our center during a 20-year period and the changes to our organ acceptance criteria during Eurotransplant membership. MATERIALS AND METHODS: We studied all kidney transplants from donors ≥60 years old during the two 5-year episodes of Eurotransplant membership from 2007 to 2017 (period II and period III) and compared those data to data from the decade before Eurotransplant membership (period I, 1997-2007). Differences in acceptance rates and reasons for the decline of kidney offers between the two 5-year periods of Eurotransplant membership were analyzed. RESULTS: In period I, 14.1% of all kidney allografts were obtained from donors ≥60 years old; in period II and period III the rates were nearly 2-fold higher (27.0% and 25.7%, respectively; P = .007 and P = .008). During the first 5-year period of Eurotransplant membership (period II), we accepted significantly more grafts from marginal donors with a higher number of human leukocyte antigen mismatches compared with period I. Consequently, the 3-month survival rate of kidneys from donors ≥60 years old dropped from 91.1% to as low as 74.2% (P = .034). After application of morestringent human leukocyte antigen matching, especially in human leukocyte antigen DR, and morestringent donor acceptance criteria in period III, graft survival improved to 91.1%. CONCLUSIONS: Our experience indicates that careful selection of kidneys from elderly deceased donors and allocation to human leukocyte antigen-matched recipients is important to improve transplant outcomes.

[Lymphocele and renal transplantation]. / Limfocele i transplantacija bubrega.

Lymphoceles are a well-known surgical complication of kidney transplantation. We retrospectively analyzed patients with lymphoceles among our renal transplant recipients. During the last 39 years, we performed 922 renal transplantations. Lymphoceles were diagnosed and treated in 45 (4.9%) patients. We used the following methods: percutaneous drainage with instillation of povidone-iodide in 36 (80%), percutaneous drainage with instillation of tetracycline in one (2.2%), percutaneous aspiration in four (8.9%) and surgical treatment in four (8.9%) patients. In all four (8.9%) patients with relapse, secondary procedure was successful. In total, open surgery was done in five (11.1%) and laparoscopy in four (8.9%) patients. Percutaneous drainage of lymphoceles, with or without the instillation of a sclerosant, is the first-line treatment. Laparoscopic fenestration of lymphoceles has become an alternative to percutaneous drainage, especially in case of post-drainage relapse.

[Surgical procedure and urologic complications after 922 kidney transplantations: our experience]. / Kirurski postupak i uroloske komplikacije nakon 922 transplantacije bubrega: nase iskustvo.

Between January 30 1971 and January 30 2011 922 kidney transplants were performed at our center, 360 (39%) from living related donor and 562 (61%) from cadaver. During first eight years an ureteroureterostomy was routinely used. The notable incidence of urological complications (fistula 11%, complications of stenting 10.7%, stenosis and lithiasis 4%) was observed after 140 transplantations. Majority of these complications (60%) were treated conservatively. A significant reduction in this incidence (P<0.001) was achieved (fistula 1,28%, complications of stenting 0,26%, lithiasis 0.12%) by introducing an extravesical ureteroneocystostomy by Lich-Gregoire. Stenosis had the highest incidence (4,23%). Majority of complications (76%) were treated surgically. A native ureter was commonly used in replacing the transplant ureter. In majority of patients an end-to-end pyelo(uretero)stomy was performed. Two patients were reoperated because of fistula, and the third had a prolonged healing. In last nine patients with urological complications an end-to-side pyelo(uretero)stomy was done. There was no urinary leakage. The safety of method results probably from an intact native ureter which has normal blood irrigation.

[The role of CT peritoneography as diagnostic tool in patient on peritoneal dialysis with dialysate leakage]. / Uloga CT peritoneografije u dijagnostici propustanja dijalizata u pacijenta s peritonejskom dijalizom.

Peritoneal dialysis (PD) can be considered as first method for dialytic treatment because improved quality of life and patient survival compared to hemodialysis. The most frequent complications of PD are peritonitis, peritoneal catheter exit site infection and mechanical complications as dialysate leakage. We present a 62 year old female patient with end-stage renal disease caused by poststreptococcal glomerulonephritis. One month after laparoscopic placement of peritoneal catheter patient started with continuous ambulatory peritoneal dialysis. Few weeks after starting the procedure enlargement of anterior abdominal wall close to the exit site of peritoneal catheter was noticed. Enlargement was disappeared after decreasing intraabdominal pressure with lowering volume of dialysate. Also, patient started with automated peritoneal dialysis (APD), but after abdominal straining enlargement of anterior abdominal wall was present again. Computed tomography of abdomen and pelvis with placement of contrast in dialysate (CT peritoneography) was performed. Imaging revealed dialysate leakage from peritoneal cavity to subcutaneous tissue. PD was temporarly stopped, peritoneal catheter removed and hernioplasty was made. After four weeks new peritoneal catheter was implanted and APD was successfully started (without dialysate leakage). CT peritoneography have important role as diagnostic tool for discovering dialysate leakage. If conservative management was unsuccessfull, surgical treatment is necessary.

Pre-transplant HLA Antibodies and Delayed Graft Function in the Current Era of Kidney Transplantation.

Delayed graft function (DGF) occurs in a significant proportion of deceased donor kidney transplant recipients and was associated with graft injury and inferior clinical outcome. The aim of the present multi-center study was to identify the immunological and non-immunological predictors of DGF and to determine its influence on outcome in the presence and absence of human leukocyte antigen (HLA) antibodies. 1,724 patients who received a deceased donor kidney transplant during 2008-2017 and on whom a pre-transplant serum sample was available were studied. Graft survival during the first 3 post-transplant years was analyzed by multivariable Cox regression. Pre-transplant predictors of DGF and influence of DGF and pre-transplant HLA antibodies on biopsy-proven rejections in the first 3 post-transplant months were determined by multivariable logistic regression. Donor age ≥50 years, simultaneous pre-transplant presence of HLA class I and II antibodies, diabetes mellitus as cause of end-stage renal disease, cold ischemia time ≥18 h, and time on dialysis >5 years were associated with increased risk of DGF, while the risk was reduced if gender of donor or recipient was female or the reason for death of donor was trauma. DGF alone doubled the risk for graft loss, more due to impaired death-censored graft than patient survival. In DGF patients, the risk of death-censored graft loss increased further if HLA antibodies (hazard ratio HR=4.75, P < 0.001) or donor-specific HLA antibodies (DSA, HR=7.39, P < 0.001) were present pre-transplant. In the presence of HLA antibodies or DSA, the incidence of biopsy-proven rejections, including antibody-mediated rejections, increased significantly in patients with as well as without DGF. Recipients without DGF and without biopsy-proven rejections during the first 3 months had the highest fraction of patients with good kidney function at year 1, whereas patients with both DGF and rejection showed the lowest rate of good kidney function, especially when organs from ≥65-year-old donors were used. In this new era of transplantation, besides non-immunological factors, also the pre-transplant presence of HLA class I and II antibodies increase the risk of DGF. Measures to prevent the strong negative impact of DGF on outcome are necessary, especially during organ allocation for presensitized patients.

[Pseudoaneurysm after renal transplantation]. / Pseudoaneurizma nakon transplantacije bubrega.

AIMS: Renal arterial pseudoaneurysm is a rare complication of renal transplantation that often causes a graft loss. A recent successful outcome of the operative treatment and a reappearance of a pseudoaneurysm and a possibility of watchful followup of pseudoaneurysm encouraged us to present our modest experience with pseudoaneurysm after renal transplant. MATERIAL AND METHODS: In our series of 843 renal transplants performed during 37 years vascular complications were observed in 57 (6.76%) patients. Pseudoaneurysm occurred in three patients (0.35%). The first pseudoaneurysm was found in 1973. A 23-year-old male patient received a double renal artery kidney from HLA identical brother. The upper renal artery was anastomosed by an end-to-end way with the internal iliac artery, and and the lower renal artery by end-to-side way to the external iliac artery. Five weeks after transplant an arteriography was performed because of the bruits heard over the transplant. A 15 x 10-mm pseudoaneurysm was revealed on the end-to-end anastomosis between internal iliac and upper renal artery. Six weeks after transplant a renal arterial resection and an end-to-side anastomosis between renal artery and common iliac artery was performed. The 38-year-old male patient received his second transplant from a 17-year-old female donor dead after craniocerebral trauma in December 2004. Two renal arteries were anastomosed separately with external iliac artery using aortic patches. Two and half moths after transplant he was admitted for an increase of creatinine level and hypertension. Color Doppler, dynamic scintigraphy and an angiography revealed a 20 x 1,3 mm aneurysmatic formation at the anastomosis of upper renal artery. The flow in the belonging part of the transplant was reduced. At surgical intervention a saphenous vein graft between internal iliac artery and renal artery was performed. Ischemia time was 15 min. The pseudoaneurysm was removed. A hole on external iliac artery was closed with a saphenal patch. The 38-year-old female patient received her second transplant in January 2005 from cadaver. There were 3 arteries. The upper polar arterywas first anastomosed to principal renal artery Then both arteries were anastomosed to external iliac artery termino-laterally. RESULTS: In the first patient a lesion of the ureteral anastomosis caused an infection, thrombosis of lower artery and a graft loss 4 months and half after transplant. The second patient was admitted urgently 3.5 months after the repair of his pseudoaneurysm because of the pain in the pelvic region. He was working that day during several hours in sitting position on his terrace. Immediate examination with color Doppler revealed a large 6 x 7-cm pseudoaneurysm medially of the transplant. An arteriography demonstrated a pseudoaneurysm with a blood leakage most likely at the site of the closure of external iliac artery with a saphenal vein patch. The arteriography showed a slower and diminished blood flow in the lower part of the transplant. At intervention the pseudoaneurysm was removed. The external iliac artery was considerably damaged and replaced with Goretex prostesis 6 mm. Unfortunately the transplant lower artery could not be saved. A microbiological examination of pseudoaneurysm in both patients was negative. In the third case we chose a watchful follow-up. Last Doppler controls show reduction of psudoaneurysm. DISCUSSION AND CONCLUSIONS: The development of a pseudoaneurysm of a transplant artery is very rare complication. Since actually ultrasonography is routinely used, a pseudoaneurysm can be easily detected. Color Doppler allows a differential diagnosis from hematoma, urinoma and lymphocele. Unfortunately a pseudoaneurysm after renal transplant often causes a loss of the transplant. The first patient had successful resection of a pseudoaneurysm, but the transplant was lost because of infection. The other patient had a subsequent pseudoaneurysm after the repair of the first. Unfortunately its repair caused an exclusion of the lower part of the kidney, but the residual renal function is satisfactory. In the third patient we chose a follow-up aware that each intervention could cause a graft loss.

Donor-specific antibodies require preactivated immune system to harm renal transplant.

BACKGROUND: It is an unresolved issue why some kidney transplant recipients with pretransplant donor-specific HLA antibodies (DSA) show a high transplant failure rate, whereas in other patients DSA do not harm the graft. We investigated whether help from preactivated T-cells might be necessary for DSA to exert a deleterious effect. METHODS: The impact of pretransplant DSA and immune activation marker soluble CD30 (sCD30) on 3-year graft survival was analyzed in 385 presensitized kidney transplant recipients. FINDINGS: A deleterious influence of pretransplant DSA on graft survival was evident only in patients who were positive for the immune activation marker sCD30. In the absence of sCD30 positivity, 3-year graft survival was virtually identical in patients with or without DSA (83.1±3.9% and 84.3±2.8%, P=0.81). A strikingly lower 3-year graft survival rate of 62.1±6.4% was observed in patients who were both sCD30 and DSA positive (HR 2.92, P<0.001). Even in the presence of strong DSA with ≥5000 MFI, the 3-year graft survival rate was high if the recipients were sCD30 negative. INTERPRETATION: Pretransplant DSA have a significantly deleterious impact on graft survival only in the presence of high pretransplant levels of the activation marker sCD30.

Association of Kidney Graft Loss With De Novo Produced Donor-Specific and Non-Donor-Specific HLA Antibodies Detected by Single Antigen Testing.

BACKGROUND: The association of donor-specific HLA antibodies (DSA) with kidney graft failure has been addressed previously; however, the majority of studies were based on small numbers of patients with graft failure. METHODS: We investigated 83 patients with failed kidney transplants for a possible association of de novo development and persistence or loss of pre-existing DSA with graft failure. Single Antigen Bead assay-detected DSA and non-DSA antibodies were compared between patients with graft loss and matched controls with functioning grafts. RESULTS: The incidence of weak de novo DSA or non-DSA at a mean fluorescence intensity of 500 or higher was higher in the graft loss than in the nonrejector group (76% vs 40%, P < 0.001). Because of the low number of patients developing de novo DSA, the DSA results did not reach statistical significance (only 22% of patients with graft loss developed de novo DSA). However, at all cutoffs, there was a significantly higher rate of graft loss in patients with de novo non-DSA. The incidence of strong pretransplant DSA that persist after transplantation was higher in the graft loss group (10% vs 1%, P = 0.034). When C1q-binding ability in sera of rejectors and nonrejectors with posttransplant de novo or persistent DSA was compared, none of the nonrejectors demonstrated C1q positivity, whereas 43% of patients with graft loss showed C1q-positive antibodies, although not necessarily donor-specific (P < 0.001). CONCLUSIONS: Our data show that the posttransplant presence of persisting or de novo HLA antibodies, especially if C1q binding, is associated with graft loss, even if the antibodies are not specific for mismatched donor HLA.

[Development of peritoneal dialysis at Rijeka Clinical Hospital Center]. / Razvoj peritonejske dijalize u Klinickom bolnickom centru Rijeka.

The dialysis population is steadily rising as a consequence of the growing incidence of terminal renal failure patients and lack of organs for transplantation. Peritoneal dialysis (PD) has become an established form of renal replacement therapy. The development of new methods, techniques, PD fluids and catheters has significantly lowered the incidence of complications and increased the use of PD throughout the world. The development of PD at Rijeka University Hospital Center, the incidence of PD patients, their underlying renal disease leading to terminal renal failure, demographic characteristics of patients, complications of treatment, and causes of discontinuation of PD treatment are described. At Rijeka University Hospital Center, PD was introduced in 1963 in patients with acute renal failure (ARF), and in 1965 in patients with chronic renal failure (CRF). Until June 2002, 149 patients were treated, 71 with ARF and 78 with CRF. Continuous peritoneal dialysis was introduced at our hospital in 1978. An increasing number of patients on continuous ambulatory peritoneal dialysis (CAPD), altogether 35, was noticed in 1999. Automated peritoneal dialysis (APD) was introduced in January 2001. Five patients were treated with this method until June 2002. The most common underlying renal diseases in patients treated from January 1999 until June 2002 were diabetic nephropathy in 13 (37.1%) and glomerulonephritis in 11 (31.4%) patients, mean age 55.5 years, range 31-75 years, both sexes equally present. The leading cause of complications were infections and the main cause of death was cardiovascular disease. Five (14.3%) patients received kidney transplants which have been functioning well in all of them. Because of the high incidence of complications during the seventies, intermittent peritoneal dialysis (IPD) was used only occasionally. A significant increase in the number of patients on CAPD was observed in 1999. By the end of 2001 almost ten percent of patients receiving dialytic treatment were on CAPD. The most common complications were peritoneal catheter exit site infection and peritonitis, which caused referral to HD treatment in four (11.4%) and death in two (5.7%) patients with impossible vascular access. The knowledge and availability of different renal replacement therapies allow the choice and application of the most appropriate treatment option in individual patients with terminal renal failure. In comparison to HD, PD improves the quality of patient's life and decreases mortality in the first years of treatment. Patients with cardiovascular disease and diabetes, whose incidence is steadily rising, have a higher incidence of complications on hemodialysis treatment. In these patients PD is preferred, especially if used as the first dialytic treatment modality. PD has also provided a means of managing patients with no possibility for vascular access for HD treatment. Infective and mechanical complications are the main obstacles during PD treatment. Adequate facilities, equipment, educated and well-trained medical personnel and appropriate selection and thorough education of patients are necessary for a successful PD program.

[Value of urinary sediment cytology in evaluation of acute tubular necrosis after kidney transplantation]. / Vrijednost citologije sedimenta mokrace u evaluaciji akutne tubularne nekroze nakon transplantacije bubrega.

AIM: The aim of the study was to assess the clinical value of urinary sediment cytology (USC) by use of phase-contrast microscopy in the evaluation of acute tubular necrosis (ATN) during the early period after kidney transplantation. The study was performed at the Cytology Laboratory, Department of Nephrology and Dialysis, Clinical Hospital Center Rijeka, Croatia. PATIENTS AND METHODS: Patients included 141 kidney recipients, 99 male and 42 female, mean age 40 +/- 13 (range 8-72) years, who had received kidney allograft during the period of ten years, and who were treated at the University Department of Internal Medicine, Rijeka Clinical Hospital Center. The majority of patients (76%) had received cadaveric kidneys. Urinary sediment was analyzed for the presence of renal tubular cells, isomorphic erythrocytes, lymphocytes, casts and debris. Renal tubular cells on USC were recognized as the most constant sign of ATN. The presence of lymphocytes should arise suspicion of rejection. MAIN OUTCOME MEASURES: A typical cytologic profile of acute tubular lesion consists of tubular cells, isomorphic erythrocytes, casts, cellular and/or amorphic debris. RESULTS: USC by use of phase contrast microscopy is confirmed as a method of a very high sensitivity (82%) and specificity (93%) in the evaluation of ATN in transplanted kidney patients during early post-transplantation period. In situations of coexistence of several causes of allograft dysfunction, "mixed" cytologic pictures were frequently created, from which it is difficult or almost impossible to identify the actual cause of kidney dysfunction. In these cases, the final judgment should be made solely by histologic evaluation, which still represents the gold standard in the evaluation of kidney allograft dysfunction. CONCLUSION: Serial USC, when thoroughly examined using phase-contrast microscopy, is a simple, noninvasive, fast, easily repeatable and inexpensive diagnostic method of high sensitivity and specificity in the evaluation of ATN during the early phase after kidney transplantation.

[Clinical use of phase-contrast microscopy in the differential diagnosis of microhematuria]. / Klinicka primjena mikroskopije s faznim kontrastom u diferencijalnoj dijagnostici mikrohematurije.

AIM: To evaluate phase-contrast microscopy in differential diagnosis of asymptomatic microhematuria in patients with asymptomatic microhematuria during the 1993-2000 period. PATIENTS AND METHODS: The study was performed at the Laboratory of Cytology, Department of Nephrology and Dialysis, Rijeka University Hospital Center, Rijeka, Croatia, and included 526 patients with asymptomatic hematuria referred from Urology Department. MAIN OUTCOME MEASURES: Presence of red blood cells (RBC), other cell types, other elements, and detritus. According to size and shape, RBCs were classified into 2 main categories: dysmorphic and isomorphic RBCs. The presence of > 80% of dysmorphic RBCs was recognized as glomerular hematuria. Isomorphic cell predominance was classified as postglomerular hematuria, and equal presence of both types was considered as mixed hematuria. RESULTS: Glomerular hematuria was found in 238 (45.2%), postglomerular hematuria in 181 (34.4%) and mixed hematuria in 22 (4.2%) patients. Additional diagnostic procedures in patients with glomerular hematuria included renal biopsy. In 89% of those patients glomerular disease was found. CONCLUSION: Phase-contrast microscopy is a simple, noninvasive and reliable diagnostic procedure in nephrology practice.

[Incidence of chronic renal failure during 35 years at the Rijeka Clinical Hospital Center]. / Incidencija kronicnog bubreznog zatajenja tijekom 35 godina u Klinickom Bolnickom Centru Rijeka.

Chronic hemodialysis treatment in the world started in 1960. At that time, due to technical development and construction of arteriovenous shunt for repeated blood access for dialysis, it was possible to treat uremia. At the Department of Surgery, Rijeka Clinical Hospital, former Dr. Zdravko Kucic Hospital, first hemodialysis was performed in 1962, whereas regular chronic dialysis treatment started in 1966. On September 20, 1966, the first hemodialysis was done in a patient with chronic uremia. A week later, the next patient was admitted for therapy. The aim of the study was to analyze demographic and other data of all patients who started dialysis in the period between 1966 and 2001. There were 910 patients, 555 (60.9%) male and 355 (39.1%) female. In the first year, only two patients were treated with hemodialysis. Until 1970, the number of new patients was 4 or 5. From 1971 till 1984 between 10 and 19 new patients started dialysis every year, and from 1985 till 1990 their number ranged from 23 to 34 per year. Further increase in the number of treated patients was recorded in 1990 when 42 patients were dialyzed. In the following years until 2001 the figures were between 40 and 58, and in 2001 55 new patients were treated. In 1966, the mean age of patients undergoing this therapy was 29.5 years, and with time it increased to 40 in 1978. From 1989 on, the mean age rose to 50, and from 1998 to 60. In 2001, the mean patient age was 63.2 years. The primary renal diseases that led to uremia in the study population were glomerulonephritis (GN) in 256 (28.1%), pyelonephritis (PN) in 165 (18.1%), diabetes mellitus (DM) in 161 (17.7%), nephrosclerosis in 111 (12.2%), uremia after transplanted kidney rejection in 47 (5.2%), polycystosis in 40 (4.4%), lupus nephritis in 12 (1.3%), other causes in 89 (9.7%), and unknown cause in 24 (2.6%) patients. The distribution of primary renal disease during the observed period was as follows: from 1966 till 1979 the cause of uremia was GN in 88 (62%), PN in 30 (21.1%), DM in only 1, polycystosis in 3, post-transplant uremia in 7, lupus in 3, and other causes in 7 patients. From 1980 to 1989, GN was the cause of uremia in 67 (31.6%), PN in 45 (21.2%), DM in 22 (10.4%), nephrosclerosis in 26 (12.3%), polycystosis in 11 (5.2%), post-transplantation uremia in 12 (5.7%), lupus nephritis in 8 (3.8%), other causes in 17 (7.9%) and unknown cause in 3 (1.9%) patients. During the 1990-2001 period, GN was recorded in only 101 (18%), PN in 90 (16.2%), DM in 138 (24.9%), nephrosclerosis in 82 (14.7%), polycystosis in 26 (4.7%), post-transplantation uremia in 28 (5.0%), lupus nephritis in 6 (1.1%), other causes in 65 (11.7%) and unknown cause in 20 (3.6%) patients. The mortality was caused by cardiac disease in 50.4%, cerebrovascular disease in 14.8%, infectious disease in 13.2%, malignancy in 7.5%, high potassium in 5.1%, gastrointestinal disease in 3.5%, other vascular diseases in 1.6%, cachexia in 1.3%, loss of blood access in 0.8%, other reasons in 1.1% and unknown reasons in 0.5% of patients. The results clearly indicate that the number of new patients grew and the mean patient age increased every year. Diabetes mellitus was the leading cause of uremia while GN and PN were less common. The main causes of death were cardiovascular diseases.

[pp65 antigenemia in evaluation of cytomegalovirus infection after kidney transplantation]. / pp65 antigenemija u pracenju citomegalovirusne infekcije nakon transplantacije bubrega.

INTRODUCTION: Cytomegalovirus (CMV) infection is the most common infectious complication after organ transplantation. Serology is useful only for detecting previous CMV infection. Dissatisfied with serologic follow-up after kidney transplantation, three years ago we introduced detection of CMV antigenemia by an immunocytochemical method using a monoclonal antibody specific for the pp65 CMV matrix protein. This test allows for quantification of positive leukocytes. The purpose of this paper is to present our three-year experience. PATIENTS AND METHODS: From May 1999 till May 2002 CMV antigenemia was examined in 76 patients: 55 patients submitted to kidney transplantation during the study period, and 21 patients previously. Antigenemia became positive at 25.68 +/- 15.51 days after transplantation. These 76 patients were divided into three groups according to the number of positive cells per 200,000 leukocytes: < 5 (group I), 6-20 (group II) and > 20 (group III). The groups consisted of 23, 20 and 11 patients, respectively. The percentage of patients treated by ganciclovir was 4.34%, 15% and 100%, respectively. In group I only one patient received ganciclovir because of geographic indication, in group II three patients because of septicemia, thrombopenia and leukopenia and previous miliary tuberculosis. RESULTS: One patient from group III with steroid diabetes died from pneumonia with abscess formation three days from admission. In another two patients, interstitial pneumonia and abscess of the arm developed. Five patients had an acute rejection episode each and were treated by high doses of methylprednisolone. Five patients had elevated temperature, transaminases were elevated in five patients, and neutropenia with or without thrombopenia was found in six patients. One patient had recurrent CMV disease and lymphocele. Two patients had preemptive treatment by ganciclovir based on positive CMV antigenemia. DISCUSSION: Various centers differ according to the approach to treatment of CMV infection, ranging from prophylaxis to deferred treatment for CMV disease. Determination of pp65 CMV antigenemia allowed us a safe follow-up of patients after kidney transplantation. Compared with previous serologic follow-up antigenemia is a considerable progress. We did not use CMV prophylaxis because it is more expensive and can cause resistance to ganciclovir. A promising novel drug valganciclovir will allow for good prophylaxis owing to its better absorption from the gut. Based on our three-year experience, optimal cut-off for antigenemia has been set at 20 positive cells per 200,000 leukocytes. The existence of symptoms or changes in the level of leukocytes, platelets or transaminases goes in favor of treatment decision. CONCLUSION: Cytomegalovirus pp65 antigenemia is a reliable tool in the follow-up of patients after kidney transplantation. Patients with primary CMV infection, those with rejection episode and threshold of 20 positive cells require preemptive treatment with ganciclovir. The measurement of pp65 CMV antigenemia has clinical, analytical and cost-effective advantages. Intensive monitoring for CMV infection allows for quick and specific detection of active CMV infection. This approach avoids resistance to ganciclovir. The method is simple and specific without expensive equipment. Avoidance of unnecessary prophylaxis adds to its cost-effectiveness.

[Evaluation and selection of candidates for renal transplantation at the Clinical Hospital Center in Rijeka]. / Ispitivanje i odabir kandidata za transplantaciju bubrega u Klinickom bolnickom centru Rijeka.

On December 31, 2001, 2486 patients with terminal renal failure received dialysis treatment in Croatia. Only one third of the patients are registered on the national waiting list for cadaveric kidney transplant. In most of the others, transplantation is impossible because of comorbidity. This is mainly due to the steadily growing age of the dialytic population and therefore a higher incidence of cardiovascular disease and diabetes. Still, evaluation of the potential recipients of cadaveric kidney transplant, registered on the waiting list, often reveals contraindications for transplantation. The aim of this study was to determine the incidence and type of contraindications in transplant candidates, found during immediate preoperative evaluation. Analysis of these data should help in determining how contraindications can be early detected and prevented. Before registering onto the national waiting list transplant candidates need to be thoroughly investigated including detailed history, physical examination, routine diagnostic procedures and additional examinations, if needed, to exclude or evaluate the possibly existing contraindications for transplantation. During the period from January 1997 until June 2002, 145 potential recipients from the national waiting list were referred to the Rijeka University Hospital Center and evaluated for kidney transplantation. Eighty-eight patients underwent transplantation. Preoperative evaluation revealed contraindications for transplantation in 52 (35.9%) candidates. Twenty-two (15.2%) patients had a positive cross-match with donor lymphocytes, 6 (4.1%) patients refused transplantation, and in 24 (16.6%) patients serious comorbidity was the reason for not being accepted for transplantation and for their withdrawal from the national waiting list. Comorbidity was mainly due to cardiovascular disease (12 patients--8.3%) and infection (8 patients--5.5%). These data show a high incidence of contraindications found during the immediate preoperative evaluation of potential kidney recipients. It was the case in more than one third of patients. During the evaluation of potential candidates for kidney transplantation special attention should be addressed to the presence of cardiovascular morbidity and infection. Peripheral vascular occlusive disease, cardiac status and/or cerebrovascular disease should be evaluated. Measures used to treat or reduce the development of complications include an optimal control of blood pressure, serum phosphate, hyperparathyroidism, dyslipidemia, and renal anemia. The sites of infection must be treated and eradicated, because immunosuppressive treatment is a threat to the transplant recipient's life. The second most common cause of refusal of potential candidates was a positive cross-match with donor lymphocytes. Sensitization to human leukocyte antigens can be prevented by the avoiding of blood transfusions and use of erythopoietin in treating renal anemia. To minimize the morbidity and mortality, the potential kidney recipients should undergo rigorous selection and thorough evaluation before including them into the waiting list for kidney transplantation. Afterwards, regular examinations are obligatory to reveal contraindications, proceed to medical interventions and treat concomitant diseases in time, which can influence the patient's survival. In case that contraindications for transplantation arise, the patient must be temporarily or definitely removed from the waiting list.