Acquired renal cystic disease: two cases of associated adenocarcinoma and a renal ultrasound survey of a peritoneal dialysis population

Long-term dialysis patients frequently develop acquired renal cystic disease (ARCD). The discovery of ARCD and renal cell carcinoma in one of our hemodialysis patients led us to review the literature. ARCD has been described mainly in the maintenance hemodialysis (MH) population. Therefore, we investigated 20 peritoneal dialysis (PD) patients for ARCD using ultrasonography. Seven patients (35%) had detectable cysts and two patients (10%) had multiple bilateral cysts. One patient had a large asymptomatic complex cyst that proved to be an adenocarcinoma. Our study suggests that ARCD is relatively common in the PD population, and we speculate that it may be related more to length of time in end-stage renal disease (ESRD) than to the mode of dialysis. The potential for malignant change appears to justify a routine screening examination with ultrasonography and/or computerized tomography (CT) to detect this recently described and probably underrecognized entity.     

Urinary tract infections per se do not cause end-stage kidney disease

The objective of this study was to determine the frequency with which urinary tract infection (UTI) in the absence of concomitant underlying abnormalities caused end-stage renal disease (ESRD). The records of 102 patients with ESRD (disease necessitating dialysis and/or transplant) seen at Children’s Mercy Hospital during a 10-year period (1986 – 1995) were reviewed. Obstructive uropathy, aplastic/hypoplastic/dysplastic kidneys, polycystic kidney disease, congenital nephrotic syndrome, acquired glomerulonephritis, idiopathic interstitial nephritis, hemolytic uremic syndrome, and a variety of systemic conditions were the cause of ESRD in 99 children; 3 children had reflux nephropathy, 1 of whom had no history of a UTI and another who had a single, afebrile UTI. A girl with a history of recurrent UTIs since 4 years of age had an elevated serum creatinine and grade II – III bilateral vesicoureteric reflux when evaluated at 8 years of age. She had ureteral reimplantations and control of the infections, but progressed to ESRD. This child appears to be the only 1 of 102 children who developed ESRD because of acquired renal injury in which UTIs were an important contributing factor. Received July 29, 1997; received in revised form October 22, 1997; accepted October 26, 1997     

Pediatric dialysis and renal transplantation in Kuwait over the past 11 years

Data on end-stage renal disease (ESRD) patients and their renal replacement therapy (RRT) were collected retrospectively from the three dialysis centers, the pediatric urology unit, and the organ transplant center of Kuwait. The study period was from 1 January 1986 to 31 December 1996. A total of 61 children, 50 of whom were Kuwaiti nationals, required RRT for ESRD during those 11 years. This gave an average annual incidence rate of 18 per million Kuwaiti children. Glomerulonephritis was the most-frequent underlying disease and accounted for 44% of total cases, while pyelonephritis (including urinary tract anomalies and dysplastic kidneys) was responsible for 30%. Multisystem disease was responsible for ESRD in 7 patients (14%), 2 of whom had lupus nephritis, 2 vasculitis, 2 Henoch-Schönlein purpura, and 1 hemolytic uremic syndrome. Continuous ambulatory peritoneal dialysis and home intermittent peritoneal dialysis, using cycler machines, were not favored dialysis techniques by most parents, especially for those <6 years old. The actuarial survival on dialysis was 75%±7% at 12 months. Of the 8 patients who died, 7 were <6 years old. Thirty-eight patients received 46 kidney transplants, 13 of which were performed on a pre-emptive basis. The actuarial patient survivals at 12 months for those receiving first live and cadaveric kidney transplants were 90%±5% and 85%±2%, respectively, while those for grafts were 76%±8% and 66%±2%, respectively. This is the first nationwide long-term study of the incidence and etiology of pediatric ESRD in our area and the RRT in a country with adequate treatment facilities.     

Donor age and graft function

We evaluated survival and renal function of cadaveric donor grafts according to donor age. The median age of the pediatric donors was 7.0 (0.7 – 16) years in 46 patients [median age 11.8 years (range) 3 – 16.8 years]. The median age of the adult donors was 34.4 (19 – 54) years in 59 patients [median age 12.1 years (range) 7 – 17.3 years]. Thirty patients were treated with azathioprine and prednisolone and 75 with cyclosporine A and prednisolone. The glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) were determined by the clearances of ⁵¹chromium-EDTA and ¹²⁵iodine-hippurate 1 – 48 months after kidney transplantation. There was no difference in graft survival between pediatric and adult grafts. There were also no differences in GFR in patients receiving grafts from pediatric or adult donors; 2 – 3 months after transplantation the GFR in recipients of pediatric grafts was 62±20 ml/min per 1.73 m² compared with 61±21 in those receiving adult grafts. The ERPF in recipients of adult grafts was significantly higher in the 1st month after transplantation: 486±239 versus 362±158 ml/min per 1.73 m². From the 4th to the 6th month after transplantation this difference disappeared: the ERPF of grafts from pediatric donors was 279±131 ml/min per 1.73 m² compared with 273±123 ml/min per 1.73 m² in grafts from adult donors. Using the single-kidney GFR and ERPF on an age-matched group of probands with minor diseases as references, 2 – 3 months after transplant the mean GFR of grafts from pediatric donors increased to 118%±51%, whereas the GFR of adult donor grafts fell to 60%±22% over the same period. After 4 – 6 months the ERPF in pediatric grafts was 96%±55% compared with 50%±22% in adult grafts. We conclude that graft survival and function in children with either a pediatric or an adult graft may not differ because graft function adapts to the requirement of the recipient. Received December 6 1995; received in revised form March 19 1996; accepted March 22 1996     

Acquired cystic kidney disease in children undergoing long-term dialysis

Acquired cystic kidney disease (ACKD) occurs in adult patients undergoing long-term dialysis. Early detection is important because clinically significant hematuria and malignancies are associated with ACKD. We evaluated by magnetic resonance imaging (MRI) and ultrasonography (US) the incidence of ACKD in 15 patients aged 7.3–21.6 years (mean 15.9 years) with non-cystic primary renal disease. Nine patients had been treated with peritoneal dialysis only, and 6 with both hemodialysis and peritoneal dialysis for 24–73 months (mean 37 months). Three patients (20%) had no cysts. In 5 patients (33%) with bilateral multiple cysts, the diagnosis of ACKD was made by MRI and US. In another 5 patients, solitary cysts were localized to one kidney by MRI, and in 2 patients solitary cysts were seen in both kidneys. This study documents that ACKD is not limited to older patients with end-stage renal disease. Early detection of these cysts can be accomplished by MRI and is warranted since 1 patient developed neoplastic tubular changes which can precede tumor formation.     

Acceptance for chronic dialysis treatment: insufficient and unequal

BACKGROUND.: Evidence suggests that a number of end-stage renal disease (ESRD)patients die without receiving dialysis. We investigated andcompared ESRD patients who died without receiving treatmentand those who were accepted for dialysis. METHODS.: All patients starting chronic dialysis in 1991 in the city ofSão Paulo and prospectively registered in the HealthSecretariat files were studied. From death certificates we obtaineddata from all patients dying with an underlying cause associatedwith chronic renal failure. Medical records from a sample ofpatients who died without receiving dialysis were reviewed. RESULTS.: Of 2127 patients, 1582 (74.4%) received dialysis and 545 (25.6%)did not. The best chance of being dialysed occurred in the 20–29age group. The age groups with the least chance of receivingdialysis were 0–9 years and over 79 years old. The oddsratio (95% Cl) of not receiving dialysis was 12.42 (6.63–23.82)times greater for patients over 60 years old compared to thoseaged 20–29 years. Patients with renal failure due to congenitaldiseases, chronic pyelonephritis, unknown cause, and hypertensionwere less likely to receive dialysis than those with glomerulonephritisor diabetes. CONCLUSIONS.: Our results suggest that many ESRD patients die without receivingdialysis. Age and cause of renal disease influence the chanceof being accepted for treatment. Restrictions of treatment needto be corrected to guarantee that maintenance dialysis willbe accessible to ESRD patients.     

Delayed acute renal failure in post-transplant period in young children from unexplained etiology

This report describes six young children (5 male) who developed delayed acute renal failure (DARF) in the early post-kidney-transplant (Tx) period in the absence of acute rejection (AR) or other diagnosable conditions. These young children, aged 16.5 ± 3.1 (12–21) months [mean ± SD, (range)] and weighing 8.5 ± 1.7 (7.1 – 11.4) kg received a primary renal Tx (5 living-related donor, 1 cadaver) between 1984 and 1992. Immunosuppression included prednisone, azathioprine, and Minnesota antilymphocyte globulin (MALG, n = 5); one patient received cyclosporine and no MALG. Initially, all patients had good urine output (UO). They became systemically ill and abruptly developed diminished UO on post-operative day (POD) 6.5 ± 1 (4 – 8). DARF was accompanied by fever (39.1 – 40.4°C, n = 6), thrombocytopenia (platelets <100,000/mm³, n = 6), leukocytosis, or leukopenia (white cell count >20,000/mm³, n = 4 or <1,000/mm³, n = 1). Four patients had diarrhea. Three had ascites and one was surgically explored for suspected urinary leak. None showed significant urinary obstruction by renal ultrasound. Renograms showed intact blood flow. Renal biopsy showed tubular ectasia (n = 6), vascular congestion (n = 5), focal glomerular endothelial swelling (n = 4), and capillary thrombi (n = 3). None showed AR. Five patients required dialysis for 11 ± 4 (7 – 15) days. All patients survived. One patient, treated for suspected AR with the monoclonal antibody OKT3, developed shock and lost her graft on POD 12 due to vascular thrombosis. Renal functional recovery in the remaining five patients took 14 ± 5 (6 – 20) days and their serum creatinine at discharge was 0.7 ± 0.5 (0.3 – 1.6) mg/dl. We report DARF from undetermined etiology occurring in the first 2 weeks of renal Tx in young children. Treatment is supportive care including dialysis. Recognition of this complication will help avoid risky investigations or unnecessary treatment for rejection. Received August 21, 1996; received in revised form February 14, 1997; accepted March 4, 1997     

Acquired renal cystic disease in children prior to the start of dialysis

This report describes the clinical course and serial sonographic findings in three children who developed acquired renal cystic disease (ARCD) prior to the institution of dialysis. The children were aged from 3 years to 13 years and their estimated glomerular filtration rate varied from 8 to 13 ml/min per 1.73 m² when ARCD was diagnosed. Their primary renal disorders, which included hemolytic-uremic syndrome and focal segmental glomerulosclerosis, had been present for 1.5–11.5 years prior to the cysts being discovered. These patients show that ARCD may develop in children with chronic progressive renal parenchymal disease prior to the institution of specific therapy for end-stage renal disease.     

Treatment of advanced renal failure: low-protein diets or timely initiation of dialysis?

Until 1996, no guidelines existed for the initiation of dialysis in patients with progressive renal failure. The publication of the National Kidney Foundation-Dialysis Outcome Quality Initiative guidelines has generated a debate on the management of advanced renal failure and the role of low-protein diets (LPDs). We performed a review of the literature to identify articles on the initiation of dialysis and LPDs, particularly those since 1996. Delayed referral of patients is widespread in both the United States and Europe, and almost 25% of patients are started on dialysis at a glomerular filtration rate (GFR) of <5 mL/min/1.73 m2. There is a high prevalence of malnutrition at the time of first dialysis, which progressively improves upon initiation of dialysis. There is no evidence regarding the efficacy or safety of LPDs in nondiabetic patients younger than 70 years old [approximately 40% of U.S. incident end-stage renal disease (ESRD) patients] and in diabetics with GFR <25 mL/min/1.73 m2 (>40% of incident U.S. ESRD). In nondiabetics who are younger than 70 years old, adherence to LPD for four to five years can be estimated to result in a delay in dialysis by 6 to 11 months. However, suboptimal energy intake is widespread in advanced renal failure, which declines further upon institution of LPD. Even nutritionally sound patients develop subclinical nutritional decline despite intense counseling. There are no data on the efficacy or safety of LPD in subgroups that constitute approximately 80% of incident ESRD patients. Concerns still exist regarding their nutritional safety in the remainder. Initiation of dialysis results in improved nutritional status and should be considered in a timely fashion.     

Prevalence of renal cell carcinoma in patients with ESRD pre-transplantation: a pathologic analysis

BACKGROUND: Acquired renal cystic disease (ARCD), renal adenoma (AD), and renal cell carcinoma (RCC) are more common in patients with end-stage renal disease (ESRD). However, the prevalence of these conditions in patients undergoing transplantation, and the clinical characteristics associated with their occurrence are unclear. METHODS: At our institution, the majority of patients undergo an ipsilateral native nephrectomy at the time of transplantation, providing a unique opportunity to study the prevalence and pathology of ARCD, AD and RCC in ESRD. We retrospectively reviewed all consecutive nephrectomy pathology reports over a six year period. Demographic and clinical characteristics associated with these lesions were identified. RESULTS: Two hundred and sixty nephrectomy reports were reviewed: ARCD, AD, RCC and oncocytoma were found in 33%, 14%, 4.2% and 0.6% of cases, respectively. On multivariable analysis, ARCD was positively associated with male sex and longer dialysis duration and negatively associated with peritoneal dialysis. Similarly, AD was positively associated with male sex, longer dialysis duration and greater age. There was a trend for RCC cases to share similar associations although the small total number of cases precluded findings of statistical significance. CONCLUSION: By pathologic analysis, renal tumors are more common in the pre-transplant ESRD population than previously reported (using radiologic methods). Our study also identifies risk factors for their occurrence. This may prove useful in designing screening studies for renal tumors in this patient population.     

Oxalate elimination via hemodialysis or peritoneal dialysis in children with chronic renal failure

. Oxalate elimination and oxalate dialysance via hemodialysis (HD) or peritoneal dialysis (CAPD) has not been studied in detail in pediatric patients. We studied plasma oxalate, oxalate elimination, and oxalate dialysance in 15 infants and children undergoing CAPD (9 female, 6 male, aged 9 months to 18 years) and in 10 children on HD (4 female, 6 male, aged 7 – 18 years). Two children in each group had primary hyperoxaluria (PH). The mean duration of dialysis prior to examination was 12±11 months in CAPD and 31±23 months in HD patients. Bicarbonate HD was performed 5 h three times a week, CAPD consisted of five daily exchanges in 5 patients and four changes in the remaining 10 children (dwell volume 40 ml/kg body weight, 2.3 g/l glucose). Although oxalate dialysance was significantly higher in HD (mean 115.6 ml/min per 1.73 m² in HD versus 7.14 ml/min in CAPD), mean oxalate elimination per week was not different between both renal replacement therapies (3,478 μmol/1.73 m² surface area/week in CAPD versus 3,915 μmol/1.73 m² per week in HD). Oxalate elimination in patients with PH was between 6,650 and 9,900 μmol/week. Plasma oxalate remained elevated in both procedures [28 – 84 μmol/l in CAPD (92/148 in PH) and 33 – 101 μmol/l in HD (70/93 in PH)]. Oxalate elimination can be increased by a more frequent hemodialysis regimen. Received May 24, 1995; received in revised form and accepted October 31, 1995     

Childhood hemolytic uremic syndrome in Argentina: long-term follow-up and prognostic features

From January 1968 to December 1984, 312 infants and children with hemolytic uremic syndrome were admitted to our unit; 8 patients died (2.5%) during the acute phase; 118 children were followed as outpatients at yearly intervals for at least 10 years (mean follow-up 13 years, range 10 – 19.8 years). Four evolution patterns at the end of the follow-up were defined: group 1, complete recovery, 74 (62.7%); group 2, proteinuria with/without hypertension, 21 (17.7%); group 3, reduced creatinine clearance, often in conjunction with proteinuria and hypertension, 19 (16.1%); group 4, end-stage renal failure, 4 (3.4%). We investigated the association between several variables of the acute stage and the long-term evolution. Most non-anuric patients recovered completely (92.5%), while 38.4% of those with 1 – 10 days and 69.2% of those with 11 or more days of anuria had chronic renal sequelae. Similar results were found when analyzing the requirement for peritoneal dialysis. Of the patients with proteinuria at the 1-year control, 86% had renal abnormalities at the end of the follow-up. In our experience, although the final outcome was not predictable in every instance, the severity of acute renal failure – as determined by the days of anuria – and the presence of proteinuria 1 year after the acute phase were the most useful prognostic indicators. Received January 9, 1996; received in revised form April 16, 1996; accepted May 10, 1996     

Renal functional reserve after acute poststreptococcal glomerulonephritis

 We evaluated renal functional reserve (RFR) in 36 patients aged 5 – 21 years, who had recovered from an acute episode of poststreptococcal glomerulonephritis (PSGN) 1 – 16 years previously, without apparent sequelae, as evidenced by normal serum creatinine, blood pressure, and urinary sediment. The control group consisted of 12 children aged 2 – 12 years with recurrent urinary tract infections or nocturnal enuresis, without active infection or anatomical anomalies. The basal creatinine clearance was similar in the PSGN and control groups: 140.0±27.4 ml/min per 1.73 m² and 142.9±15.5 ml/min per 1.73 m², respectively. The RFR in the PSGN group was significantly reduced compared with that of the control group: 18.6±12.9 ml/min per 1.73 m² and 41.1±25.3 ml/min per 1.73 m², respectively (P <0.02). In 7 PSGN patients (19.4%), no RFR was found. In 69% of patients who had recovered from PSGN more than 10 years before the protein loading tests, a significantly reduced RFR (less than 10% of baseline) was found. The same degree of reduction in RFR was found in only 26% of patients who had suffered from PSGN less than 10 years ago. Received May 23, 1996; received in revised form November 11, 1996; accepted November 27, 1996     

Effects of deflazacort immunosuppression on long-term growth and growth factors after renal transplantation

Deflazacort is an oxazoline compound derived from prednisolone. We studied changes in kidney function, growth velocity, weight/height ratio, insulin-like growth factor (IGF-I), and IGF binding proteins before and after substitution of deflazacort for methylprednisone in 27 transplanted patients aged 3.1 – 20 years. Methylprednisone (mean±SEM 0.17±0.01 mg/kg per day) was replaced by deflazacort (0.29±0.01 mg/kg per day) for a period of 1 – 5 years. Calculated creatinine clearance did not change significantly during deflazacort treatment. Growth velocity increased from 2.6±0.5 cm/year to 5.2±0.7 cm/year (1st year) in 14 prepubertal patients. After 4 years of deflazacort treatment, height standard deviation score for chronological age did not change in 7 prepubertal patients. Mean weight/height ratio decreased by 50% (1st year) and remained reduced during follow-up. Serum IGF-I, IGF binding protein -3 (IGFBP3), IGF/IGFBP3 molar ratio, and IGF-I and -II binding capacities showed no significant change; however in 5 of 6 patients IGFBP2 decreased during deflazacort therapy. Our findings suggest that immunosuppressive treatment with deflazacort is as effective as methylprednisone and may lead to an improvement in the growth prognosis of children with renal transplantation. Received May 13, 1996; received in revised form and accepted November 20, 1996     

Post-dysenteric hemolytic uremic syndrome in children during an epidemic of Shigella dysentery in Kwazulu/Natal

We report 81 of 107 cases of hemolytic uremic syndrome (HUS), admitted between July 1994 and February 1996, following an outbreak of Shigella dysenteriae type 1 dysentery in Kwazulu/Natal. All patients, excluding 1, were black with a mean age of 38 months (range 1 – 121); 50 (61.7%) were males. The mean duration of dysentery was 11.3 days (range 1 – 41) and HUS 15 days (range 1 – 91). Most patients had acute oliguric renal failure (90.1%); 42 (51.6%) required peritoneal dialysis. Complications included encephalopathy 30 (37.0%), convulsions 12 (14.8%) and hemiplegia 2 (2.3%), gastrointestinal perforation 8 (9.9%), protein losing enteropathy 26 (32.1%), toxic megacolon 4 (4.9%), rectal prolapse 5 (6.2%), hepatitis 11 (13.6%), myocarditis 5 (6.2%), congestive cardiac failure 3 (3.7%), cardiomyopathy 3 (3.7%), infective endocarditis 1 (1.2%), septicemia 15 (18.5%), disseminated intravascular coagulation 17 (21%). Leukemoid reactions were found in 74 (91.3%) patients, hyponatremia in 56 (69.1%), and hypoalbuminemia in 67 (82.7%). Stool culture for Shigella dysenteriae type I was positive in only 7 (8.6%) patients; Shiga toxin assays were not performed. Outcome was as follows: recovery 32 (39.5%), impaired renal function 8 (9.9%), chronic renal failure 26 (32.1%), end-stage renal disease 1 (1.2%), and death 14 (17.3%) patients. Received November 26, 1996; received in revised form and accepted April 15, 1997     

Renal cell carcinoma in peritoneal dialysis patients

Renal cell carcinoma is a rare but serious complication in ESRD patients. In these patients the incidence of renal cell carcinoma (RCC) is 20-40 times higher than in the general population. We performed a retrospective study to measure the incidence rate, prevalence, characteristics and survival among our peritoneal dialysis (PD) patients diagnosed with renal cell carcinoma. The study was carried out among 607 patients who were on the PD program from January 1997 to June 2002. RCC was detected in eight patients (four males and four females) with mean age of 52.1 +/- 10.6 years. Among these eight patients four were new cases that were diagnosed before the patients were started on dialysis (three in native kidneys and one in a transplanted kidney). In the other four patients the RCC was diagnosed after they had been on dialysis for 33-204 months (mean 60.75 +/- 50.48). We found an incidence rate of 1.3 per 1000 patients per year and a prevalence of 1.3%. Six of the eight patients had renal cysts. Tumor size was less than 7 cm in seven patients and in the other patient it was 8.5 cm. Seven of eight patients were alive at the time of study with a survival time ranging from 3-138 months (mean 122.25 +/- 88.2) months. In one patient, the RCC metastasised to the scalp, and, in two other patients, the tumors subsequently involved the second kidney. A cardiovascular complication was the cause of one death. Two patients received a renal transplant 36 and 66 months after diagnosis. We conclude that despite the low rate of metastases and mortality in our study, regular ultrasonography should be added to the follow-up of PD patients. Renal transplantation can be considered in these ESRD patients with RCC; however, close follow-up for metastases is recommended.     

Automated peritoneal dialysis as the modality of choice: a single-center, 3-year experience with 458 children in Mexico

Automated peritoneal dialysis (APD) has been considered as the ideal dialysis modality for pediatric patients. This study reports the 3-year APD experience with 458 end-stage renal disease (ESRD) children who started APD in a single pediatric center in Mexico City between June 2003 and June 2006. By June 2003, there were 310 patients being treated with continuous ambulatory peritoneal dialysis (CAPD). At that time, these patients were gradually switched to APD, with priority being given to those prescribed more than four exchanges per day, younger than 6 years of age, or presenting complications [hernias or decreased ultrafiltration (UF)]. An improvement of daily UF was observed when the patients were switched from CAPD (590 ± 340 ml/day) to APD (846 ± 335 ml/day). The presence of edema decreased (from 67% to 8%) as well as the percentage of patients requiring antihypertensive drugs (from 83% to 38%), the peritonitis rate improved from one episode every 35 patient/month to one episode every 47 patient/month, the total number of hospitalizations decreased (from 384 to 51), and 85% of children attended school. While waiting for renal transplant, APD is the dialysis modality of choice for ESRD children at the La Raza Medical Center in Mexico City. Dr. Divino Filho is an employee of Baxter Health Care and holds stock in the company.     

The 1998 report of the Japanese National Registry data on pediatric end-stage renal disease patients

We carried out a nationwide survey on patients less than 20 years of age with pediatric chronic end-stage renal disease (ESRD) in Japan for the year 1998. There were 582 patients who had started on renal replacement therapy before 1998, and 105 patients who had been newly introduced to renal replacement therapy in that year. The prevalence rate of the ESRD patients already on treatment was 22 per million population (aged 0–19 years) in 1998. Older patients had a higher prevalence rate than younger ones. There were 345 patients on dialysis as of 1 January 1998, and 237 patients with transplants. The major diseases causing ESRD were renal hypoplasia/dysplasia and focal segmental glomerulosclerosis. Of the 237 patients (46.9%) who had received renal transplants before 1 January 1998, 262 patients (96%) received their transplants from living kidney donors. The incidence rate for the new ESRD patients was 4 per million population (aged 0–19 years) in 1998. Older patients had a slightly higher incidence rate than younger ones. Peritoneal dialysis was used more frequently than hemodialysis under 15 years (85%–95% and 39% respec-tively), especially in very young patients. The major diseases causing ESRD were the same as in the patients already on treatment. The transplant rate for the year 1998 was 10 per 100 dialysis patient-years (patients aged 0–19 years) with 9 living kidney donors. The death rate was 15.6 per 1,000 dialysis patient-years (patients aged 0–19 years); the major causes of death being cardiovascular diseases and infections. Received: 30 January 2001 / Revised: 3 January 2002 / Accepted: 4 January 2002     

Bullous dermatosis of end-stage renal disease: a possible association between abnormal porphyrin metabolism and aluminium

BACKGROUND.: Bullous dermatosis (BD) is becoming increasingly recognizedin patients with end-stage renal disease (ESRD). It is clinicallyreminiscent of porphyria cutanea tarda, but its detailed pathogenesisremains unclear. Studies have shown increased porphyrin levelsin dialysis patients, and this may partly explain the skin lesionsand photosensitivity evident in these patients. In experimentalstudies, aluminium can induce various abnormalities in porphyrinand haem metabolism. This study investigated a possible involvementof porphyrin metabolism and aluminium in the development ofbullous dermatosis in chronically dialysed patients. METHODS.: Three groups were studied (12 healthy controls; 12 patientson chronic dialysis without BD and six patients on chronic dialysiswith BD). Clinical characteristics of these patients were evaluatedand the levels of plasma porphyrins, erythrocyte porphyrinsand enzymes involved in the porphyrin chain were determined. RESULTS.: The patients with BD were predominantly male, 50% had ADPKD,all had been on dialysis for a long period of time (7.8±2.1years) and all were anuric. CAPD and haemodialysis were usedequally in the affected patients. Aminolaevulinic dehydrataseactivity was significantly reduced in all ESRD patients (892±47versus 302±36 versus 408±37 nmol/ml RBC/h). Plasmauroporphyrins as well as RBC proto-porphyrin were significantlyelevated in ESRD patients (1.7±0.6 versus 21.6±4.7versus 43.4±12.0 nmol/l) and (1.43±0.14 versus2.4±0.42 versus 4.19±2.44 µmol/l) respectively.Serum Al levels were markedly elevated in patients with BD (28.3±10.0µg/l). Both uroporphyrin and protoporphyrin were significantlymore elevated in ESRD patients with BD compared to ESRD patientswithout BD. CONCLUSIONS.: Elevated plasma porphyrin levels in ESRD patients are causedby lack of urinary excretion and the inability of haemodialysisand CAPD therapy to remove them. These elevated porphyrin levelsmay lead to the development of porphyria cutanea tarda symptoms.Elevations in plasma uroporphyrin, red blood cell protoporphyrin,and elevated Al levels suggest a possible relationship betweenan Al ‘load’ and abnormal porphyrin metabolism inthe development of overt skin disease in the dialysed patient.     

Effect of hyperparathyroidism on response to erythropoietin in children on dialysis

The response to recombinant human erythropoietin (rHuEPO), 50 units/kg thrice weekly, was studied prospectively in 17 children and adolescents with end-stage renal disease who were either transfusion dependent or had hematocrits <25%. For convenience, rHuEPO was given intravenously to 12 hemodialysis (HD) patients and subcutaneously to 5 peritoneal dialysis (PD) patients. Blood pressure, hematocrit, iron indices, and serum potassium, calcium, phosphorus, alkaline phosphatase, urea nitrogen, and intact parathyroid hormone (PTH) were monitored serially. When serum ferritin was <100 ng/ml during therapy, 6 patients received iron supplementation. rHuEPO therapy eliminated frequent transfusions in all patients; 11 of 17 patients reached the target hematocrit of 30% – 33% by week 16 of rHuEPO, 50 units/kg thrice weekly. The 5 PD patients treated subcutaneously reached target at week 6±1; 6 HD patients treated intravenously reached target at week 11±3; 6 additional HD patients never reached target at this dose; 5 of 6 had pre-rHuEPO serum PTH levels >400 pg/ml, significantly higher than those of the other patients (P <0.005); 3 of 6 later reached a hematocrit of 30% – 33% after the rHuEPO dose was increased to 120 – 130 units/kg thrice weekly. We conclude that most pediatric dialysis patients can be treated successfully with rHuEPO, 50 units/kg thrice weekly, unless the serum PTH concentration is markedly elevated, in which case a higher dose is likely to be needed. Received May 8, 1997; received in revised form September 16, 1997; accepted September 19, 1997