Clinical characteristics and outcomes of adenovirus infection of the urinary tract after renal transplantation.

BACKGROUND: Urinary tract infection caused by human adenovirus (HAdV) after renal transplantation (RT) results in graft loss because of concomitant nephropathy and acute rejection and may result in death because of systemic dissemination. METHODS: We assessed the time period between RT and disease onset, symptoms, treatment details, disease duration, renal graft function, outcomes, and complications. RESULTS: HAdV infection of the urinary tract occurred in 8 of 170 renal transplant recipients. Symptoms were macrohematuria in all 8 patients, dysuria in 7, and fever in 5. The median period from RT to disease onset was 367 (range, 7-1763) days, and the median disease duration was 15 (range, 8-42) days. The mean serum creatinine (sCr) level prior to onset was 1.35 ± 0.48 mg/dL and the mean maximum sCr level during disease was 2.34 ± 1.95 mg/dL. These values were increased by ≥25% in 5 patients. The mean sCr levels when symptoms resolved was 1.54 ± 0.67 mg/dL, and no significant difference was seen before, during, or after disease onset (P = 0.069). Two patients were diagnosed with HAdV viremia and 1 with acute tubulointerstitial nephritis revealed on biopsy. In addition to a reduction in immunosuppressant dosage, 2 patients received gammaglobulins and 5 received ganciclovir. CONCLUSION: Symptoms of all patients were alleviated, although some patients developed nephritis or viremia. Hence, the possibility of exacerbation should always be considered. Adequate follow-up observation should be conducted, and diligent and aggressive therapeutic intervention is required to prevent the condition from worsening.

Strategic hand assistance for effective and safe retroperitoneoscopic live donor nephrectomy.

Hand-assisted laparoscopic live donor nephrectomy has been widely applied, because it enables safe dissection of the renal vessels, reducing warm ischemia time (WIT) during rapid extraction of the kidney. In the method described in the current series, the hand-port device was placed after the kidney was mostly mobilized using a pure retroperitoneoscopic procedure. After placement of the hand port, the ureter was completely dissected by an open procedure. Finally, the renal vessels were dissected and transected under the hand-assisted retroperitoneoscopic procedure, and the kidney removed through the hand port. We performed 66 retroperitoneoscopic live donor nephrectomies, including 14 right-sided and 52 left-sided procedures, with this original method of hand assistance. The mean operative time, WIT, blood loss, and renal vein length were 246 +/- 43 minutes, 209 +/- 124 seconds, 202 +/- 180 mL, and 17.4 +/- 6.4 mm, respectively. Comparison of the operative data between the initial 30 cases and the recent 36 cases using the established method showed significant differences in blood loss and WIT that approached statistical significance. No delayed graft function was observed in the current series. The technical and functional outcomes were acceptable. The site and timing of hand assistance minimize the disadvantage of a small working space during the retroperitoneoscopic procedure, making surgery easier and safer.

Transplantation of ABO-incompatible and living unrelated donor-recipient combinations.

INTRODUCTION: According to the Japanese renal transplant registry 2005, 834 transplantations were performed using living donors. Among them 199 (23.9%) kidneys were donated from spouses (husband/wife) and 174 (20.9%) from ABO-incompatible donors. This study summarized our experience of ABO-incompatible and living unrelated, especially spousal kidney transplantation. PATIENTS AND METHODS: We performed 44 cases of living donor kidney transplantation (LKT) between April 2003 and July 2007, including 14 (31.8%) from spouses (unrelated donor) who were divided into two groups: six patients (group 1; G1) from ABO-incompatible donors and eight patients (group 2; G2) from ABO-compatible donors. During the induction phase, tacrolimus or cyclosporine, mycophenolate mofetil, and methylprednisolone were used for immunosuppression. Basiliximab was administered on postoperative days 0 and 4. In all G1 patients plasmapheresis was performed to remove anti-AB antibodies prior to LKT, and splenectomy performed at the time of or before LKT. RESULTS: Among G1, no patient died. Among G2, one patient died with a functioning graft due to a traumatic subdural hematoma. Graft survival rate was 100% in both groups. The incidence of acute rejection was 33.3% and 25.0% in G1 and G2, respectively. No patient experienced a lethal infectious complication. CONCLUSIONS: Our results demonstrated that transplantation from an ABO-incompatible spousal donor was equivalent to transplantation from an ABO-compatible spousal donor. In response to the shortage of deceased donors, LKT between married couples and from ABO-incompatible donors will spread in Japan.

Preemptive kidney transplantation of living related or unrelated donor-recipient combinations.

INTRODUCTION: According to the Japanese renal transplant registry 2005, 834 transplantations were performed using living donors. Among them 112 (13.4%) patients were transplanted from living donors before the initiation of maintenance dialysis. Preemptive kidney transplantation (PreKTx) has been associated with improved allograft and patient survival rates compared to non-PreKTx. This study was designed to summarize our experience with PreKTx. PATIENTS AND METHODS: From April 2003 to July 2007, 44 living kidney transplantations were performed at our institution. We divided these 44 patients into two groups: 5 (11.4%) patients (group 1; G1) who underwent PreKTx and the other 39 patients (group 2; G2) who received kidneys after the institution of maintenance dialysis. Living unrelated donors were mostly spouses. During the induction phase, tacrolimus or cyclosporine, mycophenolate mofetil, and methylprednisolone were used for immunosuppression. In ABO-incompatible cases, plasmapheresis was performed to remove anti-AB antibodies prior to transplantation and splenectomy at the time of or before transplantation. RESULTS: Among G1, no patient died. Among G2, two patients died with functioning grafts, one due to a traumatic subdural hematoma and another due to malignant B cell lymphoma. Death-censored graft survival rates were 100% in both groups. The incidence of acute rejection was 20.0% and 20.5% in G1 and G2, respectively. CONCLUSIONS: Our results demonstrated that PreKTx from a living donor was equivalent to the non-PreKTx. However, there were also potential benefits to PreKTx in the long-term outcome, including avoidance of morbidity associated with dialysis and access procedures, as well as reduced cost. In response to the shortage of deceased donors, PreKTx from living donors will spread in Japan.

Chloroform deposition in renal cyst fluid of hemodialysis patients with renal cystic disorders.

Chronic exposure to chloroform (CHCl3) induces renal neoplasms in rodents and may be carcinogenic in humans, but studies on chronic CHCl3 deposition in the human body have not been performed. In this study, we examined 27 hemodialysis patients with renal cystic diseases including acquired cystic disease of the kidney (ACDK) accompanied by renal tumors at high frequency. Intracystic and serum CHCl3 concentrations were determined using a headspace gas chromatography/mass spectrometry analysis. CHCl3 was not detected in the serum in any cases, but levels ranging from <0.1 to 0.659 mg/L were found in the cyst fluid in most cases, including patients with ACDK and autosomal dominant polycystic kidney disease. Because intracystic CHCl3 deposition was not confined to ACDK cases, we were unable to evaluate the relationship between CHCl3 accumulation and carcinogenesis in ACDK. However, our results suggest that compounds such as CHCl3 accumulate in renal cyst fluid in hemodialysis patients with renal cystic diseases.

Contact dermatitis in dairy cattle caused by calcium cyanamide.

Nine of 250 cows on a dairy farm initially developed severe dermatitis on parts of their bodies that touched the floor, and it then spread over their entire body. The cause was suspected to be calcium cyanamide, which had been added to the material spread on the floor to prevent environmental mastitis. Experimental exposure of the skin of a cow to calcium cyanamide induced the same type of contact dermatitis, and histopathological investigations showed that it caused irritant and allergic reactions. To identify the cause of the dermatitis, a patch test with calcium cyanamide and its breakdown products, cyanamide, urea and ammonium bicarbonate, was carried out on four cows. Three of them had a positive reaction to calcium cyanamide and cyanamide; delayed and amplified reactions suggesting an allergic response were observed.

Prevention of Late-Onset Cytomegalovirus Infection and Disease in Donor-Positive/Recipient-Negative Kidney Transplant Recipients Using Low-Dose Valganciclovir.

BACKGROUND: The main challenge with cytomegalovirus (CMV) prophylaxis in IgG donor-positive/recipient-negative (D+/R-) kidney transplant recipients is late-onset CMV disease. We evaluated a novel protocol for the prevention of late-onset CMV infection and disease in D+/R- organ recipients. METHODS: Our prospective, observational, cohort study included 100 adult kidney transplant recipients. Prophylaxis with low-dose valganciclovir (450 mg/d, 3 times a week for 6 months) was administered to D+/R- recipients. Risk factors for CMV infection and disease were identified. Renal function and the outcomes of CMV infection and disease were compared between D+/R- (n = 15) and recipient-positive (R+; n = 81) organ recipients. RESULTS: D+/R- recipients showed significant independent risk factors with high hazard ratios for CMV infection (2.04) and disease (10.3). The proportion of CMV infection in D+/R- and R+ recipients was 80% and 46% (P = .023), and that of CMV disease was 33% and 6.2% (P = .008), repectively. D+/R- recipients developed CMV infection and disease within 6 months after transplantation. However, both CMV infection- and disease-free survival rates beyond 1 year post-transplantation defined as late-onset were stable in D+/R- recipients. Moreover, serum creatinine levels at 1 year post-transplantation were comparable between D+/R- and R+ recipients (1.45 ± 0.71 vs 1.16 ± 0.35 mg/dL, P = .26). CONCLUSION: Our novel protocol prevented late-onset CMV infection and disease beyond 1 year post-transplantation in D+/R- recipients.

Steroid Withdrawal Using Everolimus in ABO-Incompatible Kidney Transplant Recipients With Post-Transplant Diabetes Mellitus.

BACKGROUND: The effectiveness of everolimus (EVR) for ABO-incompatible (ABOi) kidney transplantation is unknown. We evaluated outcomes of conversion from steroid to EVR in ABOi kidney transplant recipients. METHODS: We performed a retrospective observational cohort study of 33 de novo consecutive adult ABOi living donor kidney transplant recipients. Desensitization was performed using 0 to 4 sessions of plasmapheresis and 1 to 2 doses of 100 mg rituximab according to the anti-A/B antibody titer. ABOi recipients were administered a combination of tacrolimus, mycophenolate mofetil, and methylprednisolone. Diabetic patients were converted from methylprednisolone to EVR at 1 to 15 months post-transplantation to prevent diabetes progression. Graft outcomes, hemoglobin A1c (HbA1c) levels, and cytomegalovirus infection rates were compared between the EVR (n = 11) and steroid (n = 22) groups. RESULTS: Mean postoperative duration was 814 and 727 days in the EVR and steroid groups, respectively (P = .65). Between the 2 groups, graft survival rate (100% vs 95.5%, P > .99), acute rejection rate (9.1% vs 18.2%, P = .64), and serum creatinine levels (1.46 mg/dL vs 1.68 mg/dL, P = .66) were comparable. Although HbA1c levels were elevated in the steroid group (5.47%, 5.87%; P = .003), no significant deterioration was observed in the EVR group without additional insulin administration (6.10%, 6.47%; P = .21). Cytomegalovirus infection rate was significantly lower in the EVR group than in the steroid group (18.2% vs 63.6%, P = .026). CONCLUSION: Conversion from steroid to EVR in ABOi kidney transplant recipients maintained excellent graft outcomes and avoided diabetes progression and cytomegalovirus infection.

Desensitization with the Use of an Antibody Removal-Free Protocol in ABO-Incompatible Kidney Transplant Recipients with a Low Anti-A/B Antibody Titer.

BACKGROUND: Desensitization for ABO-incompatible (ABOi) kidney transplantation mainly comprises removal of antibodies with the use of apheresis and suppression of antibody (Ab) production with the use of rituximab. This study aimed to estimate the outcomes of ABOi kidney transplantation with the use of an Ab removal-free protocol to avoid complications associated with apheresis. METHODS: A total of 32 de novo consecutive adults who underwent ABOi living-donor kidney transplantation were retrospectively evaluated. Our protocol for ABOi recipients was stratified and fixed according to the anti-A/B Ab titer at baseline before desensitization. Desensitization was performed before transplantation with 0-4 sessions of plasmapheresis or double-filtration plasmapheresis and 1-2 administrations of rituximab at 100 mg/body. Graft outcomes, anti-A/B Ab titer, and plasma fibrinogen level were compared between the Ab removal (n = 21) and Ab removal-free (n = 11) groups. RESULTS: Between the Ab removal and Ab removal-free groups, the graft loss rate (4.8% vs 0.0%; P = 1.0), acute rejection rate (19.0% vs 0.0%; P = .14), and serum creatinine level (1.74 vs 1.40 mg/dL, P = .53) were similar. The anti-A/B Ab titer was maintained at a low level until postoperative month 12 in both groups. The plasma fibrinogen level on the operation day was significantly lower in the Ab removal group than in the Ab removal-free group (163.4 vs 250.2 mg/dL; P < .001). CONCLUSIONS: Desensitization with the use of an antibody removal-free protocol for ABOi kidney transplant recipients with a low anti-A/B Ab titer can maintain excellent graft outcomes and avoid postoperative bleeding risk.

Effective and Safe Reduction of Conventional Immunosuppressants Using Everolimus in Maintenance Kidney Transplant Recipients.

BACKGROUND: Adverse events due to conventional immunosuppressive therapy decrease both graft and patient survival. We aimed to establish a new protocol using everolimus (EVR) to safely minimize conventional immunosuppressants in maintenance kidney transplant recipients. METHODS: A total of 86 consecutive kidney transplant recipients with no complications were maintained with triple-drug combination therapy (conventional group). In case of complications, the administration of very low-dose tacrolimus (C0: 5.0 to <3.0 ng/mL), reduced mycophenolate mofetil (1000-1500 to 500-1000 mg), and EVR (C0: 3.0-5.0 ng/mL) and methylprednisolone withdrawal (2-4 to 0 mg) were simultaneously conducted (EVR group). Graft survival and acute rejection rate were compared between groups. Within the EVR group, the dose of conventional immunosuppressants was compared between pre- and post-EVR administration. Renal function was evaluated 1 year post-EVR administration. RESULTS: All grafts survived in the conventional (n = 50) and EVR (n = 36) groups, and biopsy-proven acute rejection rate exhibited no significant difference between these groups (12% vs 17%; P = .55). Furthermore, no acute rejection occurred post-EVR administration. In the EVR group, all immunosuppressants significantly decreased post-EVR administration compared with those pre-EVR administration (P < .01), and serum creatinine significantly improved at postoperative year 1 (P = .031). CONCLUSIONS: EVR administration enables very low-dose tacrolimus administration, helps reduce mycophenolate mofetil and steroid withdrawal, and ameliorates renal function in maintenance kidney transplant recipients experiencing complications associated with conventional immunosuppressive therapy.

Selection Criteria for Kidney Laterality in Retroperitoneoscopic Living Donor Nephrectomy and the Usefulness of Pretransplant Intervention.

OBJECTIVES: To evaluate the selection criteria for kidney laterality and the usefulness of pretransplant intervention in living donor nephrectomy. METHODS: We compared conventional and revised criteria. The conventional criteria were that left kidneys were chosen in preference and provided the kidney with the fewest structural abnormalities and lowest functional decline and that most renal arteries remained in the donor. From April 2013, we allowed the use of left kidneys with double renal arteries. Patient characteristics and surgical outcomes were retrospectively compared between right and left retroperitoneoscopic living donor nephrectomies. RESULTS: We compared data for 30 right kidney and 222 left kidney nephrectomies. Right kidneys were selected because of multiple renal arteries (n = 18), structural abnormalities (n = 10) of the left kidney, or functional decline (n = 2) of the right kidney. Right retroperitoneoscopic nephrectomies were associated with significantly longer operating times (267 minutes vs 241 minutes), larger blood losses (240 g vs 55 g), and higher open conversion rates (10% vs 0.9%). Pretransplant intervention was necessary for structural abnormalities in right kidneys, but the amended selection criteria resulted in fewer right nephrectomies. Pretransplant intervention was still necessary by ex vivo arterial anastomosis for multiple left renal arteries, which increased the total ischemia time (94 minutes vs 64 minutes); however, post-transplantation renal function was not significantly different. CONCLUSIONS: Pretransplant intervention was beneficial both for repairing structural abnormalities and for reducing the difficulties of retroperitoneoscopic living donor nephrectomy.

Retroperitoneoscopic living donor nephrectomy: a safe and minimally invasive procedure for the donor.

A living kidney donor surgery must be safe and minimally invasive. In addition the removed kidney must be in good condition. Retroperitoneoscopic nephrectomy has the advantage that it does not risk intra-abdominal organ injuries and provides direct access to the renal artery/vein despite the small working space. An abdominal wall-lifting method combined with the pneumoretroperitoneum provides sufficient space to use a hand skillfully in retroperitoneoscopic surgery. Introduction of hand-assisted retroperitoneoscopic living donor nephrectomy with the abdominal wall-lifting method yielded safer and easier operations as well as shorter warm ischemia (mean: 3 minutes; 7 seconds) and operative times (mean: 3 hours; 28 minutes) in the current 10 cases. The procedure is a useful alternative to procure a kidney graft.

Impact of Renal Transplantation and Nephrectomy on Urinary Soluble Klotho Protein.

BACKGROUND: Klotho is a single-pass transmembrane protein predominantly expressed in the kidneys. The soluble form of klotho has been shown to participate in various pathophysiological activities. However, information regarding the kinetics of soluble klotho remains limited. We herein assessed serial changes in the amounts of 24-hour urinary excreted soluble klotho among renal transplant recipients and concomitant living donors before and after transplantation. METHODS: A total of 15 recipients and donors were included in the current study, and the amounts of urinary soluble klotho were quantified using a sandwich enzyme-linked immunosorbent assay. RESULTS: Urine samples were available in 6 of the 15 recipients prior to the procedure. The amounts of urinary klotho in these 6 recipients and overall living donors at the baseline were 58.6 ng/day (IR: 29.3-142) and 698.8 ng/day (IR: 62.3-1619.5), respectively. Those in the recipients on postoperative day 2 (median 522.3 ng/day; IR 337.1-1168.5, P < .05) and day 5 (median 723.2 ng/day; IR 254.7-1238.6, P < .05) were significantly higher than the baseline values. Among the living donors, only a transient increase was observed in the amounts of urinary klotho on postoperative day 2. CONCLUSION: The current data regarding the urinary soluble klotho in recipients support the hypothesis that the kidney is a major source of urinary soluble klotho among the numerous components of the urinary tract. In living donors, the complex nature of events associated with acute reductions in the renal mass may modulate the release of soluble klotho from the kidneys into the urine.

Comparative study of cytomegalovirus (CMV) antigenemia assay, polymerase chain reaction, serology, and shell vial assay in the early diagnosis and monitoring of CMV infection after renal transplantation.

BACKGROUND: Early diagnosis of cytomegalovirus (CMV) infection, which is an important cause of morbidity and mortality in renal transplant recipients, remains of great importance. This prospective study was performed in kidney transplant recipients to determine the diagnostic value of the CMV antigenemia assay in comparison with polymerase chain reaction (PCR), serology, and shell vial assay. METHODS: Seventy-five consecutive renal transplant recipients were enrolled in this study and monitored by both antigenemia assay and serology. The initial 34 of the 75 patients were subjected to PCR and shell vial assay. RESULTS: Antigenemia, PCR, and shell vial assay became positive before the onset of CMV-related symptoms in 31/34 (89%), 13/16 (81%), and 2/16 (13%), respectively. None of the 34 patients who had symptomatic CMV disease showed a significant increase in IgG or IgM before the onset of symptoms. Antigenemia and PCR assays turned positive, 7 and 11 days (median), respectively, before the onset of clinical symptoms. Serology and shell vial assay became positive 21 and 25 days (median), respectively, after the onset of CMV-related clinical symptoms. To examine the clinical value of these assays, "good correlation" was defined based on the correlation between the clinical course and the results of the assays. Good correlation with the antigenemia assay was observed in 33 (96%) out of 34 renal transplant recipients who recovered from their CMV disease after ganciclovir therapy. Only one of 16 (7%) patients showed good correlation by shell vial assay, whereas PCR and serology did not show a good correlation. Consequently, antigenemia was considered the best way to monitor CMV infections after kidney transplantation. CONCLUSIONS: Only the CMV antigenemia assay can be successfully employed after renal transplantation for the early diagnosis and extensive monitoring of active CMV infection.

Long-term results of ABO-incompatible living kidney transplantation: a single-center experience.

BACKGROUND: Despite great efforts to promote the donation of cadaveric organs, the number of organ transplantations in Japan is not increasing and a serious shortage of cadaveric organs exists. These circumstances have forced a widening of indications for kidney transplantation. For this purpose, ABO-incompatible living kidney transplantations (LKTs) have been performed. Although we have already reported the short-term results of ABO-incompatible LKT, there is no report of long-term results in such cases; anti-A and anti-B antibodies could cause antibody-induced chronic rejection and result in poor long-term graft survival. In this study, we have reviewed the long-term results of ABO-incompatible LKT and tried to identify the most important factors for long-term renal function in ABO-incompatible LKT. METHODS: Sixty-seven patients with end-stage renal failure underwent ABO-incompatible living kidney transplantation at our institute between January, 1989, and December, 1995. The mean age was 34.9 years (range, 8-58 years), with 38 males and 29 females. Incompatibility in ABO blood group antigens was as follows: A1-->O, 23 patients; B-->O, 19 patients; A1B-->A1, 7 patients; B-->A1, 8 patients; A1-->B; 4 patients; A1B-->B, 4 patients; A1B-->O, 2 patients. The number of HLA-AB, and -DR mismatches were 1.6+/-1.1 and 0.76+/-0.6, respectively. Plasmapheresis and immunoadsorption were carried out to remove the anti-AB antibodies before the kidney transplantation. In the induction phase, methylprednisolone, cyclosporine, azathioprine, antilymphocyte globulin, and deoxyspergualin were used for immunosuppression. Local irradiation of the graft was performed at a dose of 150 rad, on the first, third, and fifth days after transplantation. Splenectomy was done at the time of kidney transplantation in all cases. RESULTS: Patient survival was 93% at 1 year and 91% at 8 years. Graft survival was 79% at 1, 2, 3, and 4 years, 75% at 5 and 6 years, and 73% at 7 and 8 years. Patient survival was not significantly different from that of ABO-compatible patients. However, graft survival was significantly different between ABO-incompatible grafts and ABO-compatible grafts. Specifically, ABO-incompatible transplant recipients experienced a significantly higher rate of early graft loss up to 3 years but showed an equivalent graft loss by year 4. Among 67 patients, 16 grafts were lost during the observation period. Loss was due to acute rejection in 5 patients, followed by chronic rejection in 5 patients and death with function in 3 patients, whereas immunosuppression was withdrawn in 3 patients due to nonimmunological reasons. Of 16 grafts lost, 15 were lost within 1 year after transplantation. Of the 67 patients, 5 died during observation. Three patients with functioning grafts died of uncontrolled bleeding due to duodenal ulcer, malignant lymphoma, and cerebral hemorrhage (one patient each). One patient died of ischemic colitis due to secondary amyloidosis and one patient of cerebral hemorrhage after graft loss due to humoral rejection. There was no fatal infectious complication, whereas 10 patients had non-tissue-invasive cytomegalovirus infection. The stepwise logistic regression model was employed to identify the most important factors for long-term renal function. Patients were subdivided into those with serum creatinine of less than 2.0 mg/dl (group 1, n=39) versus those with serum creatinine of more than 2.0 mg/dl (group 2, n=22) at one year after renal transplantation. Six patients were excluded because of death with functioning graft (three patients) and withdrawal of immunosuppression (three patients). Rejection episodes within 6 months were significantly frequent in group 2 compared with group 1 (P=0.0008). Odds ratio was 112-fold in the rejection episodes. Obviously, the high incidence of early humoral rejection is caused by ABO incompatibility, because ABO-incompatible grafts experience a higher rate of early rejection and graft loss compa

Contributory metabolic factors in the development of nephrolithiasis in patients with medullary sponge kidney.

Whether specific metabolic abnormalities are related to nephrolithiasis in patients with medullary sponge kidney (MSK) remains a debated issue. The purpose of this study is to determine metabolic disorders in patients with MSK and nephrolithiasis compared with idiopathic calcium-stone-forming patients. One hundred eighty-four patients with recurrent calcium-stone formations were investigated with regard to metabolic abnormalities. Of these, 22 patients (11.9%; 13 men, 9 women) showed MSK by radiological examination. MSK was defined as a kidney that presented at least three linear or round papillary opacities in the affected papilla on urography. Multiple stones (more than five) existed in both kidneys in all patients with MSK. The remaining 162 patients (109 men, 53 women) were idiopathic calcium-stone formers. Frequencies of low urine volume (urine < 1,500 mL/24 h) and hyperoxaluria (oxalate > 40 mg/24 h) were similar between the groups. Hypercalciuria (men, calcium > 300 mg/24 h; women, calcium of 250 mg/24 h) was found less frequently in the MSK group. The frequency of hypocitraturia (citrate < 300 mg/24 h) was significantly greater in the MSK group than the idiopathic group (77.3% versus 33.9%, respectively). Mean 24-hour urinary excretions of calcium, citrate, uric acid, and magnesium were significantly less in the MSK group. No differences were found in serum calcium, phosphate, and parathyroid hormone levels between the groups. Low urinary excretions of citrate and magnesium are the most typical metabolic disorders that distinguish MSK stone patients from idiopathic calcium-stone-forming patients. In addition to such anatomic abnormalities as ectatic collecting ducts, low levels of urinary inhibitors of stones seem to contribute to the pathogenesis of nephrolithiasis in patients with MSK.

Metabolic risk factors in patients with first-time and recurrent stone formations as determined by comprehensive metabolic evaluation.

OBJECTIVES: To determine whether patients with recurrent calcium stone formation have more significant metabolic abnormalities compared with patients with first-time stone formation as determined by a comprehensive metabolic evaluation. METHODS: We investigated metabolic abnormalities in 37 patients (14 men, 23 women) with first-time and 136 patients (83 men, 53 women) with recurrent calcium stones, stratified according to sex. Calcium oxalate supersaturation indexes of Tiselius (1991) and Ogawa (1996) were also compared between the groups. In addition to the specific metabolic abnormalities, we analyzed the total number of such defects for each group. RESULTS: In men, the average number of metabolic abnormalities in each patient was greater in patients with recurrent stones (2.20+/-0.86) than in those with first-time stones (1.46+/-1.27). Such a difference could only be demonstrated for women if low urine volume was excluded as a specific abnormality. Although the frequency of each abnormality was higher in patients with recurrent stones, a statistically significant difference was only noted in the frequency of hypocitraturia between women with first-time and recurrent stone formation (11.1% versus 37.8%, P < 0.05). There were no significant differences in the calcium oxalate supersaturation indexes between first-time and recurrent stone formation in either men or women. CONCLUSIONS: Women with recurrent stones have a higher prevalence of hypocitraturia than women with first-time stones. Potassium citrate therapy for prevention of urolithiasis may be especially useful for this patient population.

A 10-year follow-up study of renal transplant recipients treated with cyclosporine. Japanese Cyclosporine Kidney Transplant Study Group.

AIM: In this report a 10-year follow-up of Japanese multicentre trial of renal transplantation using cyclosporine is described. MATERIAL AND METHODS: A total of 1,323 recipients, including 1,055 (79.7%) living donor (LD) transplantations and 268 (20. 3%) non-heart-beating cadaveric donor (CD) transplantations, were enrolled in the study. RESULTS: Favorable results; graft survival at 1, 5 and 10 years were 95.8%, 80.9%, 56.8%, respectively, for LD, and 88.7%, 74.2%, 58.8%, respectively, even for CD, were obtained. No serious adverse reactions or complications were observed in this group of patients excepting 28 cases (2.0%) of malignant tumors. There were no cases of abnormality in 49 babies delivered during the term. CONCLUSION: We demonstrate the interesting findings that graft survival of non-heart-beating CD are surprisingly as good as that of LD and the safety issues are almost equal to other available data in other countries.

Renal osteopontin expression in experimental urolithiasis.

Although osteopontin (Opn) is a strong inhibitor of calcium oxalate crystallization in vitro, its role in stone formation in vivo is unknown. We investigated the renal expression of Opn in normal, ethylene glycol (EG), and EG + ammonium chloride-treated rats. Male Sprague-Dawley rats were divided into three groups. Group 1 (N = 5) was the control. Animals in Group 2 (N = 6) received 4 weeks of treatment with 0.75% EG, and Group 3 animals (N = 6) were given 1 week of treatment with 0.75% EG and 1.0% NH4Cl. The kidneys were then examined for crystal deposition and Opn localization. In normal rats, staining for Opn was evident in the proximal tubules (PT; S3 > S2 > S1), distal tubules (DT), and the thick ascending limbs of Henle (TAL) and a few collecting ducts (CD). All rats in Group 3 had significant crystal deposition throughout their kidneys. In Group 2 rats, Opn staining increased in all segments of the PT, DT, and TAL. Staining in these tubular segments was even greater in Group 3 rats, including the CD and the papillary surface epithelium. In addition, Opn was present within all crystal deposits. Renal Opn expression in experimental urolithiasis becomes stronger and more diffuse as the severity of the lithiasis-inducing treatment increases. These results are consistent with the hypothesis that renal epithelial cells produce larger amounts of osteopontin to combat the development of kidney stones.

Role of the renal collecting system in initial kidney stone formation.

BACKGROUND: The anatomic site where the initial kidney stone grows to a clinically significant size is unknown. METHODS AND MATERIALS: We studied human forniceal anatomy by microdissection and correlated the anatomic findings with the clinical presentation of kidney stones. In addition, we examined crystal attachment sites within the collecting system by direct infusion of calcium oxalate crystals into the renal pelvis of rabbits. RESULTS: Secondary urinary dead spaces were found in the fornices of compound papillae only, which were located at the poles of the kidneys. This feature correlated with a higher incidence of stones in these areas at the time of lithotripsy. Calcium oxalate crystals tended not to attach to either the renal papilla nor the pelvic sidewall unless these epithelia were previously injured with hydrochloric acid. CONCLUSION: The renal collecting system may serve as an anatomic site for crystal retention and growth but is unlikely to be the principal site for crystal attachment, unless prior cellular injury occurs.