Acquired renal cystic disease in children and young adults on maintenance dialysis

Acquired renal cystic disease (ARCD) is a well-known complication of end-stage renal disease (ESRD). We studied 24 patients, aged 8 – 27 years (mean 19.8±5.3 years), on chronic maintenance dialysis in our service. The duration of dialysis ranged between 13 and 192 months (mean 77.8±44.3 months). High-resolution ultrasonography revealed ARCD in 11 (45.8%) patients. No cysts were seen in 7 (29.1%) patients and solitary cysts in one or both kidneys were seen in 6 (25%) patients. Renal malignancy was diagnosed in 2 patients. One, 15 years old, had renal cell carcinoma after being on dialysis for 6 years. She did well after bilateral nephrectomy, left salpingo-oophorectomy, and regional lymphadenectomy. The second patient, 23 years old, had been on dialysis for 16 years when she developed renal oncocytoma. She died of congestive cardiomyopathy 6 months later. We conclude that ARCD is common in children and young adults with ESRD. Neoplastic transformation, although rare, is a potential complication. Annual follow-up with ultrasonography with selective use of computed tomography or magnetic resonance imaging is advised. Received July 29, 1996; received in revised form and accepted November 15, 1996     

End-stage renal disease in a patient with congenital lymphangiectasia and lymphedema

Congenital lymphangiectasia with lymphedema is a disorder constituting the main defect in many different genetic syndromes. Herein we describe a 23-year-old male patient with congenital lymphangiectasia and severe lymphedema of the right leg, scrotum, and abdominal wall, who presented with end-stage renal disease, presumably due to cystic renal lymphangiectasia, and is undergoing chronic hemodialysis treatment. Received: 19 April 2000 / Revised: 4 October 2000 / Accepted: 5 October 2000     

Exercise-induced acute renal failure in a patient with renal hypouricemia

We describe a case of exercise-induced acute renal failure (ARF) in a patient with hypouricemia. Following recovery from ARF, the patient’s serum urate concentration was 0.6–0.9 mg/dl, and the ratio of urate clearance to creatinine clearance (C _ua/C _Cr) was 41.9%–56.6%. There was no change in the C _ua/C _Cr following the administration of pyrazinamide or probenecid, suggesting defects of tubular urate/anion exchangers. Because the renal biopsy revealed acute tubular necrosis without uric acid crystals, the ARF of this patient might be due to oxygen free radicals resulting from exercise stress and hypouricemia. Received: 15 March 1999 / Revised: 10 September 1999 / Accepted: 14 September 1999     

Length of time on dialysis prior to renal transplantation is a critical factor affecting patient survival after allografting

Within the past year at our transplant center we have had the experience of performing renal allografts in two patients older than 65 years, each of whom had been on hemodialysis more than 10 years. Both resulted in patient mortality within 90 days of transplant (one due to myocardial infarction, the other due to visceral ischemia with infarction). This prompted us to review retrospectively our own data (n = 204) and the national (UNOS) data (n = 10 971) regarding transplant outcome, patient age, and length of time on dialysis prior to renal transplantation. This review revealed that patient mortality after transplant increased with the length of end-stage renal disease (dialysis, regardless of type) independent of age, the greatest mortality occurring within the first 6 months of transplant (and not thereafter); graft survival was similar for all age cohorts analyzed. Our review of the literature reveals a paucity of articles pertaining to post-transplant mortality and length of time on dialysis prior to transplant. Our results indicate the following possible conclusions. (1) The length of time of end-stage renal disease therapy prior to renal transplantation is a significant and independent risk factor for post-transplant mortality. (2) Higher priority should be given to this factor when formulating strategies for allocation of scarce resources. (3) Patients on dialysis for extended periods of time who are elderly may be at particularly high risk. (4) Patients being considered for renal transplant should be informed of their individual risk factors for mortality post-transplant based on length of ESRD therapy. (5) Renal transplantation should be considered as early as possible in patients with ESRD (or imminent ESRD).     

Obstructive airway disease caused by Moraxella catarrhalis after renal transplantation

We report a case of severe acute obstructive airway disease 2 months after renal transplantation in a 16-year-old patient with Biedl-Bardet syndrome who was transplanted for end-stage renal failure secondary to cystic kidney disease. Symptoms of severe obstructive airway disease developed 2 months after transplantation under immunosuppression with prednisone, azathioprine, and tacrolimus. The patient did not develop signs of infection; progressive shortness of breath remained the only symptom for several weeks. After extensive diagnostic evaluation, bronchoalveolar lavage revealed Moraxella catarrhalis as the single infectious agent. After 3 weeks of appropriate antibiotic therapy, symptoms of obstructive airway disease were completely relieved. This atypical presentation of Moraxella infection in an immunocompromised host represents a rare complication of renal transplantation, especially in young patients. Special aspects such as frequency, diagnosis, differential diagnosis, and management of this rare complication of renal transplantation in a pediatric patient are discussed. Received: 22 July 1999 / Revised: 24 November 1999 / Accepted: 28 November 1999     

Experience with deflazacort in children and adolescents after renal transplantation

Deflazacort (DFZ) has been proposed as an alternative drug for immunosuppression after renal transplantation (TX), with fewer side effects than conventional glucocorticoids. We investigated renal function, body growth, body fat, and bone mineral density (BMD) after switching from oral methylprednisolone (MPR) to equivalent doses of DFZ 1–9 years after TX in 20 patients aged 5–20 years, selected because of severe adverse effects from previous steroid therapy. At conversion the patients received a mean dose of 7.4±2.4 mg DFZ/m² per day. The drug was continued for a mean of 3.7 (1.2–5.5) years. Under DFZ, the glomerular filtration rate dropped slightly (NS). A single rejection episode occurred. Growth velocity significantly improved in the 1st year on DFZ treatment and height standard deviation score (SDS) increased steadily after introduction of DFZ (from –2.64 to –1.96 after 4 years, P=0.06). However, in 10 prepubertal children the height gain (+0.20 SDS in 2 years on DFZ) was not significant and the overall mean annual growth rate after TX was similar to that in 10 matched prepubertal TX children on continued MPR treatment. Relative obesity, estimated from mean body mass index corrected for height, was reduced from +1.11 SDS at the start of DFZ to +0.71 SDS after 2 years (P=0.03) and to +0.39 SDS after 4 years (NS). BMD-SDS of the lumbar spine (L_2–4) increased after 1 year on DFZ (P=0.005). In conclusion, DFZ is well tolerated and safe in pediatric patients after TX. It improves relative obesity and bone mineralization. However, body growth is not significantly influenced pre puberty. Received: 19 October 1999 / Revised: 28 February 2000 / Accepted: 28 February 2000     

Chromophobe cell renal carcinoma with acquired cystic disease of the kidney in a long-term hemodialysis patient

We report a rare case of chromophobe cell renal carcinoma found in a 52-year-old female who had received hemodialysis therapy for 13 years. She was diagnosed as having a left renal tumor 7.5 cm in diameter with acquired cystic disease of the kidney (ACDK) by ultrasonographic examination during periodical systemic screening. As abdominal computed tomography scanning and enhanced color Doppler ultrasonography suspected that the hypervascular tumor was renal cell carcinoma, she underwent translumbar nephrectomy in July 2000. The histopathological diagnosis was chromophobe cell carcinoma with pT2 and grade 2 malignancy. Chromophobe cell carcinoma is uncommon among renal tumors with ACDK found in long-term hemodialysis patients.     

Diabetes mellitus in patients with infantile cystinosis after renal transplantation

Diabetes mellitus is a frequent long-term complication of infantile nephropathic cystinosis. We studied 44 cystinotic patients, aged 22.1±5.4 years, transplanted at a mean age of 11.3±2.5 years; 25% were treated with insulin at 20 years of age or 10 years after transplantation, and over half required insulin at latest follow-up. In comparison, diabetes mellitus occurred in only 1% of non-cystinotic transplanted patients. Sequential oral glucose tolerance tests (OGTTs) in these patients showed the progressive deterioration of glucose metabolism. All but 2 patients had an abnormal response at latest follow-up. The high doses of corticosteroid given after transplantation or during rejection episodes were responsible for transient insulin dependency. However, the development of impaired glucose tolerance and diabetes mellitus depended mainly on the cystinotic process, which developed slowly with time. The deterioration of glucose tolerance was correlated with a decreased early phase of insulin secretion, estimated from the plasma insulin level at 30 min of the OGTT, while there was no evidence of insulin resistance. The occurrence of diabetes mellitus correlated with a worsening of the vital prognosis. Received: 28 July 1998 / Revised: 22 September 1998 / Accepted: 23 September 1998     

Unilateral renal cortical necrosis with contralateral hydronephrosis after surgery for uterus carcinoma

Renal cortical necrosis (RCN) represents a rare cause of acute renal failure that is characterized by necrosis of the renal cortex with sparing of the medulla. Most previous RCN cases reported have been bilateral and have occurred in pregnancy. Unilateral RCN is a quite rare disorder. Here, we report a case of unilateral RCN with contralateral hydronephrosis after surgery for uterus carcinoma. In this patient it seems that hydronephrosis had been present before RCN occurrence. It is suggested that ureteric obstruction protects against RCN development. Received: July 7, 2002 / Accepted: November 8, 2002 Present address: NIH/NIDDK, Bldg. 10, Room 4D51, 10 Center Drive-MSC 1370, Bethesda, MD 20892, USA Tel. +1-301-435-6582; Fax +1-301-435-6587 e-mail: Seijih@intra.niddk.nih.gov Acknowledgments The authors gratefully acknowledge the help of Tianxin Yang, MD, PhD, Jurgen Schnermann, MD (Laboratory for Renal Function and Development, NIDDK, NIH, Bethesda, MD, USA) and Josie Briggs, MD (Director, DKUHD, NIH, Bethesda, MD, USA). Correspondence to:S. Hashimoto     

Chromophobe renal cell carcinoma and 'capsulomas' with acquired cystic disease of the kidney in a long-term hemodialysis patient

Abstract:   Patients receiving long-term hemodialysis tend to develop renal cell carcinoma (RCC). Among such cases, chromophobe RCC and so-called 'capsulomas' are rarely reported. Here, we report a case of a Japanese woman in her early 70s, who developed both renal lesions after 17 years of hemodialysis. The patient received radical nephrectomy for enlarging renal mass. Grossly, the resected kidney showed a dominant tumor and small-sized subcapsular nodules. Histologically, two types of neoplasm, chromophobe RCC and 'capsuloma', existed with acquired cystic disease of the kidney. Chromophobe RCC had eosinophilic cytoplasm with perinuclear halos, and some tumor cells showed oncocytic features. Hale's colloidal iron staining showed a weakly positive cytoplasmic reaction. Immunohistochemistry was diffusely positive for cytokeratin 7, but negative for vimentin in the tumor cells. 'Capsulomas' were multiple subcapsular nodules composed almost entirely of smooth muscle-like cells with immunoreactivity for melanosome-associated antigen detected by HMB-45.     

Pretransplant blood transfusions with cyclosporine in pediatric renal transplantation

Pretransplant transfusions were repeatedly shown to be associated with improved graft survival in the ”pre-cyclosporine era,” and have recently been shown to be beneficial in patients on modern immunosuppressive regimes. In an attempt to improve this transfusion effect and minimize the potential development of cytotoxic antibodies, we have given these transfusions, with concomitant cyclosporine cover, prior to transplantation. Ninety-two renal transplantations were performed in 91 children in the study group (group 1) and all received pretransplant transfusions with cyclosporine cover. Results were compared with a preceding group of 102 children (104 transplantations) who had received pretransplant transfusions without cyclosporine cover (group 2). There were 70 cadaver and 22 living-related donor (LRD) transplants in group 1, and 88 cadaver and 16 LRD transplants in group 2. Graft survival rates (1- and 5-year) for cadaver transplantation were 96% and 90% in group 1 compared with 78% and 64% in group 2 (P=0.001). For LRD transplantation, these figures were 95% and 87% in group 1 and 81% and 69% in group 2. There was no difference between the two groups in terms of age at transplantation, sex, donor age, HLA-A, -B, -DR mismatches, or cold and warm ischemia times. All cadaver graft recipients received quadruple, sequential immunosuppression post transplant. However, 9 patients in group 1 were changed to tacrolimus for recurrent rejection episodes. No patient developed persistent lymphocytotoxic antibodies post transfusion or side effects of cyclosporine. Cyclosporine can be safely given with whole blood prior to transplantation with no adverse effect and no sensitization. Graft survival was significantly improved in this group of patients and graft loss due to rejection was exceptional. This effect should be further evaluated in prospective studies. Received: 10 June 1999 / Revised: 9 March 2000 / Accepted: 10 March 2000     

Effects of growth hormone on growth factors after renal transplantation

Growth retardation occurs frequently in renal transplanted children (RTx) and can be improved by growth hormone (GH) treatment. This study retrospectively examines the insulin-like growth factor-1 (IGF-1) and IGF binding protein (IGFBP) profile of ten growth-retarded children previously given renal allografts, after 1 year of GH treatment period. Ten prepubertal patients (nine boys and one girl) were investigated. They had a mean chronological age (CA) of 11.4±1.1 years and a mean bone age (BA) of 7.3±0.9 years. Mean height was –3.9±0.4 SD units below the mean for CA. The mean body mass index (BMI) was 16.9±0.6 and the mean inulin clearance was 36.5±4.9 ml/min/1.73 m². Recombinant hGH was given at 4 IU/m²/day. Plasma GH, total and free IGF-1, IGFBP-2 and -3 were measured by specific radioimmunoassay (RIA). IGFBPs were characterized by SDS PAGE techniques and ligand and immunoblot analyses. Mean velocity was markedly increased (P<0.01) after 1 year of GH therapy, expressed as SD score for BA. The range of growth response was wide. The total and free plasma IGF-1 increased (P<0.01) by about 100% (mean values after GH therapy: 95.9± 2.1 nM and 165±29 pM, respectively). Plasma IGFBP-3 concentrations increased by about 40% (mean value: 148±18 pM, P<0.01), with a concomitant increase in both intact IGFBP-3 and its 30-kDa proteolytic fragment. There was no change in plasma IGFBP-2 concentration. Both mean values of inulin clearance and BMI were unchanged during the treatment. In view of the IGF-1/IGFBP concentration changes, there should have been an even better growth response to GH therapy in these patients. This strongly suggests IGF-1 insensitivity, probably as a result of corticosteroid therapy. Received: 12 April 2000 / Revised: 31 July 2000 / Accepted: 1 August 2000     

Gastroduodenal lesions and Helicobacter pylori in children with end-stage renal disease

Thirty-seven children with end-stage renal disease were evaluated for gastroduodenal lesions by upper gastrointestinal endoscopy between January 1993 and January 1998. The mean (±SD) age of the patients was 14.3±2.4 years (range 9–17 years). Endoscopic examination was abnormal in 17 patients (46%). The lesions were antral gastritis plus bulbitis (n=6), nodular bulbitis (n=4), antral gastritis (n=4), and duodenal ulcer (n=3). Fifteen patients had symptoms related to gastroduodenal disease, whereas 22 patients were asymptomatic at the time of endoscopic examination; 80% of the symptomatic and 23% of the asymptomatic patients had gastroduodenal lesions on endoscopy. Antral mucosal biopsy was taken from 26 of 37 children for the detection of Helicobacter pylori by the urease test. H. pylori was detected in 10 of 16 patients with gastroduodenal lesions (8 symptomatic, 2 asymptomatic). None of the patients with normal endoscopic examination were positive for H. pylori. Thus, we have demonstrated a significant number of gastroduodenal lesions and their frequent association with H. pylori in our pediatric renal transplant candidates. Our results emphasize the importance of gastrointestinal evaluation in these patients. Endoscopic examination should be considered in symptomatic patients and in areas where H. pylori is endemic. Received: 17 September 1998 / Revised: 27 October 1999 / Accepted: 28 October 1999     

Towards guidelines for dialysis in children with end-stage renal disease

There are few data describing the current practices of treatment selection for children with end-stage renal disease (ESRD). In an effort to establish a consensus among Spanish pediatric nephrologists for inclusion and exclusion criteria for renal replacement therapy in children with ESRD, in 1995 we surveyed members of the Spanish Pediatric Nephrology Association. Although only 43% of members responded, pediatric nephrologists and bioethicists studied the results and compiled a list of ten guidelines for treatment of children with ESRD. The proposed guidelines are meant to be a starting point for further discussion. An emphasis on flexibility, individual case assessment, and consideration of the best interests of the patient must remain central to any treatment plan. Decision making should ideally be shared by parents, professionals, the child, when appropriate, and ethics committees, as necessary. Received: 9 February 1999 / Revised: 21 June 1999 / Accepted: 28 June 1999     

Long-term outcome of focal segmental glomerulosclerosis after Japanese pediatric renal transplantation

Focal segmental glomerulosclerosis (FSGS) is known to recur in some patients after renal transplantation. Over a prolonged period, we followed 13 pediatric patients with FSGS who had undergone transplantation from living-related donors, analyzing risk factors for recurrent disease. Native nephrectomies were performed bilaterally in all patients at least 1 month prior to transplantation. Immunosuppressive therapy consisted of cyclosporine (CyA), mizoribine, prednisone, and antilymphocytic globulin or deoxyspergualin. We examined age at onset, time in months between diagnosis and end-stage disease (dialysis or transplantation), the duration of dialysis, age at transplantation, time since nephrectomy, doses of immunosuppressive agents, and HLA mismatch. Five patients (42.8%) developed recurrent disease in the graft; all showed proteinuria within 24 h of transplantation. However, all allografts have functioned well for 34–156 months following transplantation despite the recurrences, although 1 of these patients now shows proteinuria. The remaining 8 patients have had no recurrence for 104.6±30.4 months (mean±SD). The serum level of creatinine in patients with recurrence and without recurrence was 1.1±0.42 mg/dl and 0.98±0.29 mg/dl, respectively. The interval from diagnosis to initiation of dialysis was significantly shorter in patients with recurrence than those without recurrence (P<0.05), but no other variables differed between these two groups. No recurrence of FSGS was observed in the protocol biopsy at 100 days after transplantation. We believe that CyA and native nephrectomy may limit or reverse progression of recurrent FSGS in renal allografts of Japanese pediatric patients, although this is a limited study. Received: 22 December 2000 / Revised: 6 September 2001 / Accepted: 10 September 2001     

Renal cell carcinoma co-existent with other renal disease: clinico-pathological features in pre-dialysis patients and those receiving dialysis or renal transplantation.

BACKGROUND: Patients on chronic dialysis are prone to developing acquired cystic kidney disease (ACKD), which may lead to the development of renal cell carcinoma (RCC). The risk factors for the development of RCC so far have not been determined in pre-dialysis patients with co-existent renal disease. The aim of this study was to evaluate the clinico-pathological features of RCC in pre-dialysis patients with associated renal diseases or in those undergoing chronic dialysis and renal transplantation. METHODS: We studied 32 kidneys from 31 patients with RCC and associated renal diseases. Of those, 18 kidneys were from 17 patients not on renal replacement therapy (RRT) when diagnosed with RCC; 14 patients received dialysis or dialysis followed by renal transplantation. Several clinico-pathological features were analysed and compared between the two groups. RESULTS: Overall, there was a preponderance of males (75%); nephrosclerosis was the predominant co-existent disease (31%). The median intervals from renal disease to RCC in the dialysis and transplanted groups were significantly longer than in the pre-dialysis group (15.8+/-1.1 vs 2.4+/-0.7 years, P<0.0001). In contrast to pre-dialysis RCC, the dialysis and transplant RCC groups had greater frequency of ACKD (100 vs 28%, P<0.0001), papillary type RCC (43 vs 11%, P<0.05) and multifocal tumours (43 vs 5%, P<0.05). At the end of the study, 71% of dialysis and transplanted patients and 72% of pre-dialysis patients were alive. CONCLUSIONS: ACKD develops in dialysis patients, as it does in those with renal disease prior to RRT. The duration of renal disease, rather than the dialysis procedure itself, appears to be the main determinant of ACKD and RCC. The RCC occurring in patients with ACKD and prolonged RRT is more frequently of the papillary type and multifocal than the RCC occurring in patients with no or few acquired cysts and a short history of renal disease. Long-term outcomes did not differ between the two groups.     

Hepatitis C infection in children and adolescents with end-stage renal disease

The prevalence of hepatitis C virus (HCV) infection and the risk factors associated with its transmission are described in a contemporary cohort of 55 children and adolescents with end-stage renal disease (ESRD). Thirty-seven patients were on dialysis or had been transplanted (ESRD) and 18 had chronic renal failure (CRF) but had not yet received dialysis. Seven (19%) tested positive for HCV by enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), or both. None of the children with CRF were infected. HCV infection was associated with length of time on dialysis, but not with age, gender, race, or units of blood transfused. These data corroborate earlier reports and confirm that children with ESRD continue to have a high prevalence of HCV. It is also shown for the first time that elevated transaminases should not be employed to predict HCV infection in this cohort, as all affected children had normal serum levels. Because of unique characteristics in this cohort, both ELISA and PCR are required to maximize HCV diagnostic sensitivity. Although HCV remains an important consideration in pediatric ESRD, the present study shows that recent advances in clinical practice have eliminated one of the major ways in which it was previously being transmitted. Received: 30 July 2001 / Revised: 2 January 2002 / Accepted: 4 January 2002     

Cystic local recurrence of renal cell carcinoma after laparoscopic radical nephrectomy in a hemodialysis patient

Although local recurrence of renal cell carcinoma after laparoscopic radical nephrectomy is sometimes reported, cystic local recurrence of renal cell carcinoma has rarely been reported. We report the case of a 59‐year‐old man with hemodialysis who developed cystic local recurrence of renal cell carcinoma accompanied by acquired cystic disease of the kidney in the retroperitoneal space after laparoscopic radical nephrectomy. A cystic tumor of 5.1 cm in diameter occurred in the left retroperitoneal space 15 months after left laparoscopic radical nephrectomy, and enlarged to 7.2 cm in diameter with enhanced mass along the wall of the cyst 36 months after surgery. The cystic tumor was removed and showed local recurrence of renal cell carcinoma on pathological examination.