[Chronic renal failure after hematopoietic stem cell transplantation]. / La nefropatia cronica post-trapianto di cellule staminali emopoietich.

Hematopoietic stem cell transplantation, autologous or allogeneic, is a well established hematology procedure. There can be a number of renal complications in this setting, which may occur in every phase but all strongly influence prognosis. Among the late complications, there is the well-known possibility of progressive chronic renal failure, appearing together with hypertension and modest alterations of the urinary sediment, and characterized by pathological findings of thrombotic microangiopathy, often without the corresponding clinical aspects. This clinical picture must be distinguished from other forms of clinically more severe thrombotic microangiopathy, such as those occurring in the early post-transplant period, and from other causes of renal disease in the hematopoietic stem cell transplantation setting. Total body irradiation, chemotherapeutic drugs, calcineurin inhibitors and opportunistic infections have all been considered as causal factors. The nosological classification is still poorly defined, as are the real prognosis and the best treatment. Kidney biopsy is a necessary tool to make a correct diagnosis, assess the frequency of the condition, make a prognostic judgment, and set up rational treatment.

Renoprotective effect of early inhibition of the renin-angiotensin system in renal transplant recipients.

The aim of this work was to study the effect of early administration of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type-I receptors blockers (ARB) on renal function and proteinuria in renal transplant recipients with good, stable renal function and mild proteinuria. Twenty four patients started ACEI/ARB therapy within 14 months after surgery (RAS-). Before (T0) and every month for 2 years after the initiation of ACEI/ARB we evaluated creatinine clearance (CrCl), proteinuria/day (UP), UP/CrCl (FUP), arterial blood pressure, and serum lipid levels. Twenty-eight patients who never received ACEI/ARB (RAS+) were studied in the same fashion. In the RAS+ CrCl was reduced after 2 years compared with T0 (64.5 +/- 2.6 vs 75.0 +/- 3.2 mL/min, P < .003); UP and FUP were both significantly increased (666 +/- 65 vs 132 +/- 20 mg/day 8.8 +/- 1.2 vs 2.6 +/- 0.6 mg/mL x 10(3); P < .001 and .002) compared with T0. Moreover, UP (P < .04), FUP (P < .03), and the percentage reduction of CrCl (11.4% +/- 5% vs 4.6% +/- 1.8%; P < .05) were greater in RAS+ than RAS- subjects at 2 years of the study. The values of other parameters did not show significant differences between the two groups. In conclusion, this study suggested that ACEI/ARB have renoprotective effects, when used in patients with good stable renal function and mild proteinuria. These drugs may play a role to prevent chronic allograft nephropathy.

Effects of successful renal transplantation on left ventricular mass.

Left ventricular hypertrophy is an independent cardiovascular risk factor in the general population and in patients with chronic renal failure. Relatively little is known about the effects of renal transplantation on left ventricular hypertrophy. The aim of this study was to determine the changes in left ventricular mass after successful renal transplantation and to evaluate the importance of some clinical, laboratory, and echocardiographic variables on the trend to left ventricular hypertrophy. Twenty-three patients with end-stage renal disease were studied by ambulatory blood pressure monitoring and echocardiography before and 2 years following renal transplantation. After 24 months of follow-up, all transplant recipients had adequate renal function (serum creatinine <2 mg/dL). At the end of the study, we observed a significant decrease in left ventricular mass and left ventricular mass index compared to the pretransplantation period. In renal transplant recipients, the prevalence of left ventricular hypertrophy significantly decreased (78% versus 44%, P < .03) after 2 years of follow-up. Systolic 24-hour blood pressure was the only predictor of left ventricular mass and of left ventricular mass index at 2 years after transplantation. In conclusion, successful renal transplantation produces a regression of left ventricular hypertrophy. This beneficial effect depends on a decrease in systolic pressure levels.

Long-term therapy for postrenal transplant erythrocytosis with ACE inhibitors: efficacy, safety and action mechanisms.

SUBJECTS AND METHODS: Eleven patients with postrenal transplant erythrocytosis were treated with angiotensin-converting enzyme inhibitors for 18 months. RESULTS: Indices of red blood cell production and destruction, renal function and kalemia were followed-up during the treatment. Angiotensin-converting enzyme inhibitors (ACEi) led to a progressive and significant fall in hemoglobin and hematocrit compared to the basal values at every time interval considered with a maximum reduction at 12th month for hemoglobin ( 17.04 +/- 0.21 vs. 15.10 +/- 0.42 g/dl, p < 0.0001) and at the 6th month for hematocrit (53.74 +/- 0.56 vs. 45.7 +/- 1.19 %, p < 0.0001). Serum erythropoietin levels were reduced significantly after the first month of therapy (13.56 +/- 2.7 vs. 7.48 +/- 1.6 mUI/dl, p < 0.05) after which no further variations were recorded. In the course of ACEi therapy, there was an inverse correlation between percentage reduction in erythropoietin values and those of hemoglobin emerged (r = 0.24, p < 0.05) and hematocrit (r = 0.39, p < 0.01). Indices of red blood destruction including haptoglobin, bilirubin and lactic dehydrogenase, were unaffected by ACE inhibitors treatment, as was creatininemia and kalemia. Treatment was well tolerated by all patients who completed the study without major adverse side-effects. No patient required phlebotomy and no thromboembolic event occurred during angiotensin-converting enzyme therapy. CONCLUSIONS: Our results suggest that angiotensin-converting enzyme inhibitors are a safe and effective long-term therapy of postrenal transplant erythrocytosis. These agents decrease the erythropoietin synthesis but this effect is not the sole mechanism by which angiotensin-converting enzyme inhibitors act in postrenal renal transplant erythrocytosis.

Insertion of a straight peritoneal catheter in an arcuate subcutaneous tunnel by a tunneler: long-term experience.

OBJECTIVE: This study describes the results of the insertion of a straight Tenckhoff peritoneal catheter (PC) in an arcuate, caudally concave tunnel using a tunneler designed by the authors. It has a semicircular shape and a bending radius of 4.5 cm. SETTING: A hospital renal unit. PATIENTS: From June 1988 to February 1994, 112 straight Tenckhoff PCs, 62 with one deep cuff (single-cuff PC) and 50 with two cuffs (double-cuff PC), were inserted as first catheters in 112 patients (mean age 62 +/- 13 years), who underwent continuous ambulatory peritoneal dialysis (CAPD). The follow-up was 1099 months (mean 18 +/- 13 months) for single-cuff PCs and 1264 months (mean 25 +/- 15 months) for double-cuff PCs, respectively. INTERVENTIONS: After intraperitoneal placement of the PCs by median laparotomy, a 180 degrees arc bend tunnel, with both external and peritoneal exits directed downwards, was created by means of the tunneler. RESULTS: The rate of exit-site infection (ESI) was 0.27 episodes/year (epis/year). The probability of remaining ESI-free was 76%, 60%, and 55% at 1, 2, and 3 years. The rate of tunnel infection (TI) was 0.046 epis/year. The incidence of the double-cuff PC-related ESI and TI tended to be lower than the incidence observed with the single-cuff PC. Episodes of peritonitis were 60 (0.30 epis/year), where 6 were subsequent to ESI and/or TI. Two PCs were lost due to ESI, 3 due to TI, and 11 due to peritonitis. Drainage failure, due to displacement of the PC caused by straightening, involved 3 PCs; 2 were lost. PC survival was 92%, 82%, and 74% at 1, 2 and 3 years, respectively. CONCLUSIONS: By an easily used semicircular tunneler, the standard straight Tenckhoff PC can be stably positioned in an arcuate tunnel with both inner and outer exits directed downwards. This tunnel shape, as already suggested by some authors, appears to be an effective technical solution to reducing the PC-related complication rates.

Renal allograft protection with early angiotensin-converting enzyme inhibitors administration.

Twenty renal transplant recipients (RTx) with a normal ultrasound pattern of renal artery who began angiotensin-converting enzyme inhibitor (ACEI) therapy within 14 months after surgery (ACEI(+)) were studied retrospectively to evaluate endogenous creatinine clearance/1.73 m(2) body surface area (CrCl), proteinuria (UP), UP/CrCl (FUP), mean arterial pressure (MBP), total cholesterol, LDL, HDL, and triglycerides. Before (T(0)) and every month for 2 years after initiation of ACEI. Twenty-four RTx who never received ACEI (ACEI(-)) were studied in the same fashion. No differences in the parameters were noted at T(0); all RTx had CrCl >60 mL/min, Up less than 0.5 g/d, and stable renal function for 3 months before the study. In the ACEI cohort CrCl was reduced after 2 years compared with T(0) (65.6 +/- 2.8 vs 76 +/- 3.2 mL/min, P <.004), UP and FUP were both increased (660 +/- 60 vs 130 +/- 20 mg/d, 8.9 +/- 1.3 vs 2.8 +/- 0.6 mg/mL x 10(3); P <.001 and.002, respectively). UP >0.5 g/d was present in three cases. After 2 years the ACEI(+) group showed a decrease in CrCl (68.2 +/- 3.1 vs 73 +/- 2.2 mL/min) and the increase in UP (181 +/- 21 vs 139 +/- 18 mg/d) and in FUP (3.1 +/- 0.7 vs 2.6 +/- 0.9 mg/mL x 10(3)), which were not significantly different from the values at T(0). No cases showed UP >0.5 g/d. Moreover UP (P <.04), FUP (P <.03) and the percent reduction of CrCl (11.2 +/- 2.5% vs 4.6 +/- 1.8%, P <.05) were greater among ACEI(-) than ACEI(+) patients at 2 years. ACEI(-) patients showed correlation between the percent reduction of CrCl and UP (r =.51, P <.04). The values of MBP and lipids did not reveal any significant difference between the two groups. In conclusion, this study suggests that ACEI have a renoprotective effect, when used early, and may also prevent chronic allograft nephropathy.

[Clinicopathologic correlations in acute renal graft rejection]. / Aspetti clinico-patologici del rigetto acuto nel trapianto renale.

Although the diagnostic and therapeutic outcome of renal transplantation has successfully improved during the last decades, acute graft rejection (AGR) is still an ongoing cause of concern being often associated with irreversible graft dysfunction. Renal biopsy remains a valuable tool in the initial assessment of the potential graft malfunction especially during the early post-transplant period. It is an accurate and sensitive means for detecting prognostically relevant microscopic abnormalities, and assisting in subsequent patient management. For long time, the histopathologic evaluation of AGR has suffered from an irreducible bias with poor interobserver rates. Nowadays, the classification schemes of AGR include the BANFF approach and the National Institute of Heath Collaborative Clinical Trials in Transplantation (NIH-CCTT) system: both have been originally designed in order to improve the diagnostic reproducibility of AGR among pathologists. Arteritis and tubulitis, along to clinical information, constitute the cardinal features of the BANFF classification. Distinguishing features of the traditional NIH-CCTT system includes microscopic criteria such as assessment of interstitial hemorrhage, extent and quality of inflammatory infiltrate, and acute glomerulitis, in addition to tubulitis and arteritis. The BANFF classification has apparently gained more popularity than the time-honored NIH-CCTT system since, if used in the appropriate clinical context, it allows a more accurate assessment of AGR, provides prognostically relevant information, and has a better reproducibility rate among pathologists. Nevertheless, the accuracy trend has not significantly improved during the last few years.

[Surgical complications after kidney transplantation]. / Le complicanze chirurgiche ed urologiche del trapianto di rene.

Chronic renal failure needs substitutive treatment such as haemodialysis and peritoneal dialysis for the patient to survive. Kidney transplantation (KTx) improves survival of the patient with chronic renal failure. Since the first KTx, performed by Merrill in Boston in 1959, advances in medical therapy, immunosuppressive therapy and refinements in surgical technique have improved the quality of life of the transplant patient. We present a review of the incidence, diagnosis and therapy of surgical complications after KTx reported in the literature and a retrospective analysis of 297 consecutive cadaveric donor kidney transplants done in our institution from September 1993 to September 2002. Vascular complications represent 5-10% of postoperative complications. Our experience showed an incidence of 1.7% renal artery thrombosis, 1.4% renal vein thrombosis, 1.7% renal artery stenosis, 1.4% arterial rupture due to fungal arteritis, 0.7% spontaneous graft ruptures and 12% lymphoceles. Urological complications account for 10-15% of postoperative complications. In our series we found an incidence of 7.4% urinary leakage, 2.7% urinary obstruction and 3% urinary reflux. Gastrointestinal complications represent 16% of postoperative complications. Our series showed 1% pancreatitis with an overall mortality of 33% and an incidence of 1.7% intestinal perforations. Surgical complications still represent a challenge that increments morbidity and mortality among kidney transplant recipients. Data shown may offer some guidance on how to deal with early and late post-transplant surgical complications.

[Cardiovascular disease after renal transplantation]. / La malattia cardiovascolare dopo trapianto renale.

Cardiovascular disease is the leading cause of morbidity and mortality following renal transplantation. Because many renal transplant recipients die with functioning grafts, deaths resulting from cardiovascular disease have became an increasingly important cause of graft loss, particularly after the first post-transplantation year. Moreover, a contribution of some cardiovascular risk factors to renal allograft dysfunction has been demonstrated. A number of observational studies suggest that cardiovascular disease is more common in renal transplant patients than in the general population. The excessive risk for cardiovascular disease is related to a high prevalence and accumulation of atherogenic risk factors before and after transplantation. Hypertension, post-transplantation diabetes and hyperlipidemia are well-recognized risk factors for the development of cardiovascular events after renal transplantation and are strongly associated with immunosuppressive therapy. Progressive renal dysfunction may also influence the risk of cardiovascular complications after renal transplantation. The elevated risk may also be caused by non- traditional risk factors such as anaemia, adhesion molecules, hyperhomocysteinemia, microinflammatory state, abnormal coagulation and oxidative stress. To prevent post-transplantation cardiovascular disease it is crucial to define the etiological risk factors. Some risk factors can be modified, and for some of these, there is strong evidence from studies in the general population that intervention improves survival. Given the significant morbidity and mortality of cardiovascular disease in renal transplant recipients, aggressive treatment intervention for potentially modifiable factors are strongly advocated after transplantation. In addition to treatment intervention, risk management should also involve tailoring the immunosuppressive regimen to minimize both direct and indirect cardiovascular risks. In this article we attempted to review and quantify the post-transplant risk factors for cardiovascular disease as well as offer suggestions on optimizing the therapy or treatment strategies to minimize the risk of cardiovascular complications in renal transplant patients. Reduction of cardiovascular morbidity and mortality can improve not only the life expectancy and quality of life of the transplant recipients but also their graft function and survival.

Balance of non-metabolizable base in continuous peritoneal dialysis patients.

Acid generation and elimination processes compared to titratable non-metabolizable base (NaOH equivalents, NB) turnover in end-stage renal disease patients are examined in the light of the Law of electroneutrality. The application over 2 days of the whole-body NB balance technique to 18 patients undergoing continuous ambulatory peritoneal dialysis is evaluated. The results show that the mean rate of NB loss with peritoneal effluent (as bicarbonate and organic acid anions) exceeded the mean rate of NB gain with the dialysis fluid (as salts of lactic acid) by 24 (27), m (SD), mmol per 2 days. In spite of this, the bicarbonate and pH of the plasma remained stable and within normal limits. The concurrent mean rate of the intestinal NB absorption was about 61 (27) mmol per 2 days, as calculated from the whole body balances of the several electrolytes in the metabolic steady-state. This intestinal absorption was more than sufficient to restore the body base consumed in neutralizing endogenous acid generation: 37 (14), 2H2SO4 mmol per 2 days, the remaining NB being eliminated as bicarbonate and organic acid anions. The ample spectrum of plasma acid-base (A B) values appears to some extent influenced by patient-related factors, such as the rate of drinking water intake and the set point deviation for organic acid turnover.

Renal involvement in acro-renal-ocular syndrome: interstitial nephritis, unlikely pyelonephritis.

We describe a case, seemingly sporadic, in which ocular and acral malformations were associated with an interstitial nephropathy; we made a diagnosis of acro-renal-ocular syndrome. There was no stasis, reflux, or urinary tract infection in our patient. We believe that interstitial nephritis in acro-renal-ocular syndrome may not always be pyelonephritis, as previously reported.

Acid production and base balance in patients on chronic haemodialysis.

Acid generation and elimination processes were compared with total base (bicarbonate plus metabolizable anions) turnover in 18 anuric patients undergoing post-dilutional haemofiltration. The study was conducted during the second haemodialysis session of the week by means of a whole-body base balance technique. The results showed that the mean rates of base loss and base gain during dialysis did not differ (i.e. the dialysis base balance approximated to zero). The concurrent mean rate of intestinal base absorption was 66+/-26 mmol/2 days, as calculated from the whole-body balance of the various inorganic cation and anion differences in a metabolic steady state. This level of intestinal base absorption would be capable of neutralizing the 59+/-21 mmol of H(+) ions/2 days that is contributed by sulphuric acid, which is the most important endogenous acid produced in anuric patients. In spite of the fact that intestinal base supply was adequate to neutralize endogenous acid production completely, our patients presented with pre-dialysis non-carbonic acidosis. The depression of plasma bicarbonate levels could not, however, be explained by increased concentrations of the anion gap and organic acids, which were within normal limits both before and after dialysis. We suggest as an alternative hypothesis that this pre-dialysis acidosis may represent an isotonic dilution acidosis that is induced by the ingestion of base-free tap water in order for plasma tonicity to be protected from the accumulation of impermeant dietary solutes, which takes place during the interdialysis period in anuric patients.

Atrial natriuretic peptide and hemodynamic changes after concentrated ascitic fluid reinfusion in cirrhotic patients.

In order to assess the role, if any, of atrial natriuretic peptide (ANP) and hemodynamic changes in diuretic response to concentrated ascitic fluid reinfusion (CAFR) in cirrhotic patients, we studied 10 patients with liver cirrhosis before and after aspiration, concentration and intravenous reinfusion of their ascitic fluid. Basal ANP levels were higher than in normal subjects, but not related to the degree of water and sodium excretion. CAFR induced a variable degree of ANP changes and diuretic response, and these two parameters were strictly correlated to each other. No major changes of cardiac output and systemic vascular resistances were observed after CAFR. In conclusion, the apparent resistance to ANP diuretic action observed in basal condition in cirrhotic patients seems to revert after expanding blood volume by CAFR.