Bilateral Small Kidneys Research Articles

Chronic renal failure in a boy with classic Bartter’s syndrome due to a novel mutation in CLCNKB coding for the chloride channel

Progressive renal failure in patients with classic Bartter's syndrome (cBS) due to inactivating mutations in CLCNKB gene is extraordinarily rare. We describe a 17-year-old Chinese boy who presented with progressive muscle weakness and renal failure. He was diagnosed as BS of unknown type at the age of 9 months and treated with indomethacin (2 mg/kg/day) and potassium chloride (KCl) supplementation (1.5 mEq/kg/day) for hypokalemia (2.5 mmol/l). At the age of 12 years, serum K+ was 3.0 mmol/l and creatinine reached 2.0 mg/dl. On admission, his blood pressure was normal but volume status was depleted. Urinalysis was essentially normal. Biochemical studies showed hypokalemia (K+ 2.4 mmol/l) with a high transtubular K+ gradient (TTKG) 9.6, metabolic alkalosis (HCO3- 28.4 mmol/l), normomagnesemia (2.0 mg/dl), severe renal failure (BUN 94 mg/dl, Cr 6.3 mg/dl), and hypocalciuria (urine calcium/creatinine ratio 0.02 mg/mg). Abdominal sonography revealed bilateral small size kidneys without nephrocalcinosis or renal stones. After the withdrawal of indomethacin with regular KCl and adequate fluid supplementation for 1 year, serum creatinine and K+ levels have been maintained at 4.0 mg/dl and 3.3 mmol/l, respectively. Direct sequencing of NKCC2, ROMK, ClC-Kb, and NCCT in this patient disclosed a novel homozygous missense mutation (GGG to GAG, G470E) in CLCNKB. This G470E mutation was not identified in 100 healthy Chinese subjects. Long-term therapy of non-steroidal anti-inflammatory drugs (NSAIDs), prolonged hypokalemia, chronic volume depletion, and underlying genetic variety may contribute to the deterioration of his renal function. The cautious use of NSAIDs, aggressive correction of hypokalemia, and avoidance of severe volume depletion may prevent the irreversible renal damage in patients with BS due to a Cl- channel defect.

Long term outcome of patients with autosomal dominant polycystic kidney diseases receiving peritoneal dialysis

There is a general perception that patients with polycystic kidney disease on peritoneal dialysis have poor long-term technique survival. In order to test this opinion, we performed a retrospective analysis comparing results of 56 consecutive patients with polycystic kidney disease to 56 non-diabetic patients with bilateral small kidneys. The patient groups were all initiated on peritoneal dialysis over a 12 year period and matched for age, gender and years of end stage renal failure. After a mean follow-up period of 37 months the two groups were statistically indistinguishable in terms of mortality, kidney transplantation-censored technique survival, median death-censored technique survival, the number of patients switched permanently to hemodialysis due to technique failure and the rate of peritonitis. On Cox regression (multivariate) analysis, only the baseline serum albumin level was a significant and independent risk factor of death-censored technique failure. Our study found no difference in long term outcome of peritoneal dialysis therapy in patients with polycystic kidney disease compared to a non-diabetic matched control group.

End-Stage Kidney Disease Probably due toReflux Nephropathy with Segmental Hypoplasia (Ask-Upmark Kidney)in Young Boxer Dogs in Norway. A Retrospective Study

This paper is a retrospective morphologic study of 7 young Boxer dogs, showing end-stage kidney lesions compatible with chronic pyelonephritis with severe segmental cortical atrophy and fibrosis, associated with chronic tubulointerstitial inflammation of varying degree. Azotemia was observed in 6 of the 7 cases. The gross kidney lesions were as follows: bilateral small kidneys with numerous segmental cortical scars causing depression of the renal cortical surface. Histologic examination revealed salient atrophy of nephrons, including paucity of glomeruli, glomerulocystic lesions, colloid-filled tubular microcysts, and a conspicuously increased occurrence of arteries with narrowed lumina caused by intimal thickening. These segmental abnormalities were accompanied by pronounced interstitial fibrosis. All but 1 dog showed salient tubulointerstitial lympho-plasmacytic infiltration, which in 3 cases also included diffuse infiltration of polymorphonuclear neutrophilic leukocyte (PMN)-cells and occurrence of tubular PMN-casts. Morphologic signs of abnormal metanephric differentiation (renal dysplasia) were observed in all cases in the form of atypical tubules or asynchronous nephronic development (immature glomeruli) or both. However, other morphologic primary dysplastic features were absent. Based on the morphologic features, it is concluded that the end-stage kidney disease in these young Boxer dogs was the result of chronic atrophic nonobstructive pyelonephritis, most probably caused by vesico-ureteral reflux, compatible with reflux nephropathy causing segmental hypoplasia (Ask-Upmark kidney) in man. It is proposed that atypical tubular epithelium in the form of adenomatoid proliferation of collecting duct epithelial cells should be considered an acquired compensatory lesion, rather than the result of disorganized metanephric development.

Glomerulopathy in Kuwait: The Spectrum over the Past 7 Years

There are few studies that examine, prospectively, the epidemiological profile of glomerulopathy (GP) and its clinicopathological correlation. All patients referred to Al-Amiri renal center in Kuwait from 01 1st, 1995 to 12 31st, 2001 were screened for GP. Detailed clinical data were collected and serological markers were done. Renal biopsy was performed whenever indicated. During those 7 years, a total of 584 patients were diagnosed, on histological basis, to have GP, 315 of whom were Kuwaiti nationals. During the same period of the study, 26 patients presented with bilateral small kidneys, history of proteinuria >2 g/day and lacked systemic manifestations of autoimmune disease. Furthermore, 164 patients with clinical manifestations of diabetic glomerulosclerosis were not subjected to kidney biopsy. Hence, the calculated annual incidence rate of GP in Kuwaiti nationals was 34.5 per 100,000 population (PTP). The calculated rate of diabetic glomerulosclerosis was 13.4 PTP and that of non-diabetic 21.1 PTP. The calculated incidence rates of GP increased with age and were twice as high in males compared to females. Vasculitis was more common in elderly males while SLE nephritis was a disease of adults, 88.7% of whom were females. In the subgroup of primary GP, focal segmental glomerulosclerosis was the most common histological lesion accounting for 18.0% of the total biopsies in Kuwaiti patients, yet only 36.8% of those who fulfilled the criteria of primary type. Minimal change disease was the second primary GP (13.0%), followed by immunoglobulin A deposition disease (7.9%) and membranous glomerulonephritis (5%). Autoimmune diseases such as systemic lupus erythematosus (SLE) and vasculitis were common. Interestingly, only 44 of 72 (61.1%) of patients with SLE and 11 of the 62 (17.7%) of patients with vasculitis presented with rapidly progressive glomerulonephritis. On the other hand, 10 of 58 (17.2%) patients with nephroangiosclerosis presented with renal failure and protein excretion >2 g/day simulating primary GP. Furthermore, only 21 of 40 (52.5%) patients with IgA nephropathy presented with “benign disease”. Prospective studies are essential to ascertain the actual incidence and etiology of GP. The loose clinicopathological correlation in GP dictates an aggressive diagnostic approach in its study and management.

Primary hyperoxaluria type 1

Primary hyperoxaluria type 1

Permcath as Temporary Vascular Access for Hemodialysis

The efficacy and complications of 30 cuffed, double-lumen silastic catheters (Permcaths) inserted in 24 patients with chronic end-stage renal failure were studied prospectively at the Security Forces Hospital in Riyadh from June 1992 until March 1996. The causes of end-stage renal failure in the 24 patients were diabetes mellitus (10), glomerulonephritis (5), hypertension (2), amyloidosis (1), and bilateral small kidneys of unknown cause (6). Local anesthesia was used in 27 and general anesthesia in 3 patients. Internal jugular, external jugular, and subclavian veins were used in 13, 12, and 5 instances, respectively. The number of dialysis sessions varied from 1 to 292, with a mean of 59 ± 60 sessions. The blood flow was 200 to 350 (280 ± 42) mL/minute. The duration of catheter function varied from 4 to 682 (150 ± 160) days. Six catheters developed poor blood flow due to thrombosis in one of the two lumens. In two, blood flow improved after use of streptokinase 15000 IU/lumen, and four had to be changed. Four patients developed exit-site infection. Staphylococcus aureus was isolated from three of these patients, and all of them improved with systemic antibiotics and local dressing. Acinetobacter was isolated from one exit site and the catheter was changed because there was no response to antibiotics. Four patients developed septicemia; S. aureus was isolated from two, Acinetobacter from one, and one had negative culture. Catheters were removed in two of these patients because there was no response to antibiotic therapy. One patient developed right internal jugular vein thrombosis. The reasons for removal of a Permcath were: poor blood flow (4), death of the patient (3), bleeding and hematoma (2), renal transplantation (2), septicemia (2), exit-site infection (1), use of arteriovenous fistula (1), patient's request (1), and primary failure (1). Eleven catheters were functioning until the end of the study. Two patients were lost for follow-up. In conclusion, Permcath can be used as a temporary as well as a long-term vascular access. It combines the advantages of being able to be used immediately and for an indefinite period that varies from weeks to months.

The spectrum of renal disease associated with microscopic polyangiitis and classic polyarteritis nodosa in Kuwait

This study was conducted to examine prospectively the epidemiological profile of renal disease associated with microscopic polyangiitis (MPA) and classic polyarteritis nodosa (classic PAN) in Kuwait and its clinicopathological correlation. Between 1 January 1993 and 31 December 1996, all patients referred to Al-Amiri renal centre were subjected to renal biopsy and/or arteriography if they manifested systemic manifestations of vasculitis or had rapid or unexplained renal failure with or without proteinuria. Patients who fulfilled the criteria of MPA and classic PAN, according to the Chapel Hill Consensus Conference (CHCC), were included in the study. Over those 4 years, 47 patients were diagnosed as having such vasculitides, 22 of whom were Kuwaiti nationals. This gave an average annual incidence of 45 cases/million adult Kuwaiti nationals (95% CI, 27-64). Histological examination revealed necrotizing glomerulonephritis (GN) in 11 patients and crescentic GN in 13, while isolated small- and/or medium-sized-arteritis were evident in six more patients. In 10 of the remaining patients; bands of fibrosis alternating with healthy renal tissue were seen and on arteriography non-atherosclerotic stenoses, infarctions, and/or microaneurysms were evident. The remaining seven patients were diagnosed by arteriography alone, five of whom had bilateral small kidneys. Constitutional manifestations of vasculitis were present in 32 patients (68%) and multisystem involvement in 19 (40%). ANCA levels were high in 24 (55%) of the 44 patients tested and seropositivity, as an antimyeloperoxidase, was a constant finding. Only six patients presented with rapidly progressive renal failure, while 31 presented with chronic renal disease, 18 of whom had protein excretion in excess of 2 g/day. These findings emphasize the limited role of clinical assessment in establishing a definite diagnosis of renal vasculitis and put in question its value in retrospective analysis of causes of ESRD in different populations.

Long-Term Followup of Renal Morphology and Function in Children With Recurrent Pyelonephritis

Renal morphology and function were evaluated in 161 children with recurrent pyelonephritis with or without vesicoureteral reflux and with or without scarred or small kidneys. The patients were followed for 1 to 21 years. Renal function was determined by glomerular filtration rate and effective renal plasma flow by clearances of inulin and paraaminohippuric acid.Of 105 children with normal kidneys originally small or scarred kidneys developed in 37, of whom 22 had grade III or greater vesicoureteral reflux, while small kidneys developed in 13 of 29 children with renal scarring originally. Of the 37 children with normal kidneys originally renal parenchymal scarring developed in 14 after the age of 4 to 5 years. Glomerular filtration rate was already <—2 standard deviations of that of controls in 51% of the patients at the first and in 53% at the last investigation of renal function. Of these patients with a glomerular filtration rate of <—2 standard deviations 69% had small or parenchymally reduced kidneys most of whom had the first pyelonephritis episode before age 3 years. Patients with small kidneys had a lower glomerular filtration rate than those with normal sized kidneys, whether scarred or not. The low glomerular filtration rate and its subsequent further reduction were related to kidney size and not to the presence or degree of vesicoureteral reflux. However, in individual patients the rate of functional deterioration could not be predicted from the radiological findings. Patients with bilateral small kidneys seemed to show the greatest decrease in glomerular filtration rate during followup as did those with grade III or greater reflux undergoing surgery bilaterally and those patients also had a lower glomerular filtration rate at the last investigation compared to patients not undergoing surgery.In conclusion, renal functional damage seems to occur early in the course of the disease and seems to be related to kidney size but there is a further slow progression with reduction in renal function which occurs, although this is difficult to predict from the radiological changes in individual patients. Therefore, patients with recurrent pyelonephritis should be followed regularly by glomerular filtration rate determination using an accurate method. Supported by grants from the Swedish Medical Research Council (No. 6864), Frimurarorden and the Karolinska Institute.

Renal dysfunction in children with vesicoureteral reflux

It is well recognized that reflux nephropathy is one of the commonest causes of end-stage renal failure (ESRF) in children. We made a retrospective study of 28 children with vesicoureteral reflux (VUR) who showed impaired renal function, as defined by either the serum creatinine of more than 1.0 mg/dl or BUN of more than 20 mg/dl. There were 20 boys and 8 girls, and the incidence of both sexes was 4.8% and 1.9% respectively. Of patients, proteinuria was detected in 22, and hypertension in 7. Five patients progressed to ESRF during his or her clinical course. About half of the patients in this series presented proteinuria or growth retardation which had led to urological check-up. Bilateral reflux was demonstrated in 24 patients, and all of the remaining 4 with unilateral reflux had hypoplastic or dysplastic contralateral kidney. Micturition cystourethrography revealed moderate or severe reflux in 86% of the ureters either at the first examination or during the follow-up periods. Urographic findings which suggested renal dysfunction included bilateral small kidney, unilateral small kidney with contralateral renal scarring, and bilateral generalized renal scarring. According to the pattern of the progression of renal dysfunction, patients were subdivided into 3 groups. Group I; patients showed bilateral renal hypoplasia on urography, and renal dysfunction progressed to ESRF before the age of 10 years despite surgical treatment. In patients of group II, gradual decrease of renal function led to ESRF at the age of puberty, although SCr was around 1.2-1.5 mg/dl when they were about 10 years old. In group III, renal function was stable at about 1.0 mg/dl of SCr during childhood. Temporary improvement of renal function was observed in only 3 of 21 children who were followed for more than 1 year after antireflux surgery. Deterioration of renal function was caused within 6 months to one year. Antireflux surgery had only little influence on the improvement of renal function in this series. We emphasize the need for early detection and management of reflux to prevent progression of renal dysfunction.

1537 RENAL INVOLVEMENT IN FANCONI'S HYPOPLASTIC ANEMIA

Fanconi's anemia is associated with multiple congenital anomalies. 28% of patients have renal abnormalities. We studied renal involvement in 2 boys and 3 girls aged 3-13 years with Fanconi's anemia. Chromosome numbers were normal but metaphases showed increased breaks and gaps in the 4 children studied. 3 children had significant growth retardation. 3 had enuresis. 1 girl had recurrent urinary infections. Initially, BP, BUN, serum creatinine, blood electrolytes, acid-base status, proteinuria, urinary concentration and acidification were normal in all. 3/4 IVPs were abnormal - bilateral small kidneys (one pelvic) with ureteric reflux (pt. 1); unilateral small kidney with ureteric reflux and clubbed calyces (pt. 2); small kidney with ureteric reflux and non-functioning small kidney on the opposite side (pt. 3). IVPs done at intervals showed no renal growth for 2 and 5 yr (pts. 2,3). Despite correction of low pressure reflux (pt. 3), renal failure was progressive. One girl (pt. 3) died awaiting renal transplant; 1 boy (pt. 4) died of unknown cause. Of the 3 children treated with androgens, 2 did not respond - 1 child died early in treatment, the other had advanced chronic renal failure. Conclusions: A variety of developmental renal abnormalities may be seen in Fanconi's anemia. Renal failure may be progressive. Anemia may respond poorly to androgen treatment if chronic renal failure is present.

腎の発育よりみた膀胱尿管逆流症

62 children and 51 adults with primary reflux were evaluated. Renal ratio (renal length/length of L2 plus its disc) of 99 refluxing kidneys of children and both kidneys of 51 adults were calculated. These values were compared to the mean and standard deviation of normal renal ratio of similar age groups, which were determined by measurement of 240 normal kidneys.1) Cases of child: 16% of refluxing kidneys were below -2 S. D, on the initial IVPs, and most of them presented a grade 3 reflux, a grade 3 ureteral orifice and an abnormality on IVP.76 refluxing kidneys were then followed for periods ranging from 1 to 8 years. Normal renal growth occurred in 68% through the priods (group 1). Renal ratio of 8 % declined temporarily below -2 S. D., although they exhibited accelerated growth and resumed normal renal ratio as soon sa spontaneous cessation or improvement of reflux occurred (group 2). All refluxing units exhibited spontaneous cessation or improvement belong to group 1 to 2, in which normal renal growth was observed.Renal ratio of another 8 % were gradually deteriorated and finally became smaller than -2 S. D. (group 3). Renal ratio of 16% were persistently below -2 S. D. on initial and also on final IVP, despite the fact that half of them underwent antireflux operation (group 4). The majority of these groups 3 and 4 presented a grade 3 reflux, a grade 3 orifice and an abnormality on IVP. However, despite normal IVP or sterile urine, deteriorated renal growth were observed in some cases. 3 cases with bilateral small kidneys showed a moderate decrease in total renal function.It is considered that -2 S. D. of normal renal ratio indicate the limit of conservative treatment and antireflux surgery is preferable, because a small kidney being for some period below -2 S. D. is unlikely to resume normal renal growth, while the small kidney exhibited accelerated growth when stopping or improvement of reflux occurred as soon as renal ratio declined below -2 S. D.2) Cases of adult: Significant difference in renal ratio between both kidneys were commonly observed, in cases with either unilateral or bilateral reflux.36% of refluxing kidneys were below -2 S. D. Two thirds of them were grade 3 reflux and one third were grade 2. But the majority presented a grade 3 orifice and an abnormality on IVP. 8 (34. 8%) cases of the 23, who had unilateral or bilateral small kidneys, were uremic. 4 cases associated with bilateral small kidneys were all uremic.This study would indicate that most of small kidneys in adults are the result of gross reflux in childhood and the function of small kidney are remarkably impaired.3) Four extremely samll kidneys removed (from one child and three adults) demonstrated microscopically almost normal nephron structure with slight mononuclear cells infiltration and the presence of partial chronic pyelonephritis. Slightly dysplastic elements (primitive ducts) were also observed in three kidneys. However, it could not be determined as to the reason why these kidneys were small: whether they were secondary to chronic pyelonephritis or congenital renal dysplasia.Finally, it was emphasized that careful observation of renal growth is also important in management of children with reflux and they should be surgically corrected before a refluxing kidney becomes smaller than -2 S. D.

Dwarfed Kidneys in Children

THE HE RADIOLOGIC demonstration of a single kidney or of bilateral small kidneys in a child presenting with signs and symptoms of renal insufficiency commonly results in the diagnosis of renal hypoplasia. However, small kidneys may be the result of many etiologic factors, including a failure of normal renal differentiation and development, disproportionate growth of the organs, and contraction secondary to scarring. It is difficult to evaluate and clearly identify which of these factors has operated to produce the small kidneys found in a given clinical problem. Furthermore, the terminology as currently applied to describe these conditions is unsatisfactory. A review of the existing literature, and the classifications and definitions which have been employed are needed. Bilateral dwarfed kidneys which on microscopic study were normal have not occurred in our experience. The small kidneys which we have studied have invariably shown histologic evidence of either dysplasia or chronic inflammatory disease