Diffuse proliferative lupus glomerulonephritis. Determination of prognostic significance of clinical, laboratory and pathologic factors.

Clinical, laboratory and pathological factors in 35 females with diffuse proliferative lupus glomerulonephritis were analyzed to determine the prognostic significance of the individual variables. The clinical and laboratory variables were age, serum creatinine (Cr), serum C3, serum C4 and proteinuria at the time of biopsy while the biopsy ones included intraglomerular monocytic infiltration (NSE index), total glomerular deposits, extent of subendothelial deposits, extent of extraglomerular deposits, tubulo-interstitial inflammation, relative tubulo-interstitial volume and total pathologic score. Standard morphometric and counting procedures were used to determine the levels of all pathologic variables but pathologic score and extra glomerular deposits where grading estimates were done. Survival curves were determined by the life table method. Logrank and chi-square tests were used to establish levels of statistical significance. Seven patients developed established renal failure (Cr greater than or equal to 2.0 on two or more occasions at least 3 months apart) and nine showed significant deterioration of renal function (decrease in CrCl of 25% or more in between biopsy and last follow-up visit or an increase in serum Cr of 0.4 mg/dl or more over the follow-up period). The 5-year renal survival rate (absence of established renal failure) for the whole group was 77%. Serum Cr (p less than .005) and extent of extraglomerular deposits (p less than .025) were shown to be significant prognostic factors for renal survival. Of the seven patients who developed renal failure none had an NSE index greater than 3.0 and one had a C3 greater than or equal to 45 mg/dl. Statistically these factors were weak prognostic indicators (0.5 less than p less than .1). Multivariate analysis demonstrated that the extraglomerular deposit factor contributed significant additional prognostic information to that provided by Cr. Although not important as a prognostic factor on its own, the NSE index significantly improved the prognostic performance of serum Cr. The product of the NSE index and serum C3 proved to be a strong prognostic factor (p less than .005).

Nephronophthisis.

Twenty-one patients with nephronophthisis are described with a follow-up of one to 16 years (mean 9.3 years). In 10 patients, there was a familial incidence. Autosomal recessive appears the likely mode of inheritance with a 20 per cent incidence noted (seven of 35) following correction for the bias of ascertainment by removing the probands. Seven patients had an associated and characteristic retinal degeneration from infancy. Associated neurologic problems, including mental retardation, seizures and cerebellar ataxis, were also seen in some patients. Previously described skeletal abnormalities and hepatic fibrosis were not seen in any of our patients. All presented at an advanced stage of chronic renal failure, usually associated with a history of polydipsia and polyuria from infancy. Renal cysts were noted in only one of the nine patients in whom tissue was obtained by needle biopsy. In seven patients in whom tissue was available at nephrectomy or autopsy, cysts were noted in six although only in two were they localized to the medulla. Eighteen patients have undergone dialysis, and 12 patients have received a renal transplant with no evidence of recurrence of the original disease. Sixteen patients are still alive. Many synonyms for nephronophthisis have appeared, with medullary cystic disease being the most common. Our experience suggests that nephronophthisis is a common cause of chronic renal failure and has commonly associated nonrenal abnormalities.

Experience with 1,25-dihydroxycholecalciferol therapy in undergoing hemodialysis patients with progressive vitamin D2-treated osteodystrophy.

Six long-term hemodialysis patients with progressive skeletal deterioration during long-term pharmacologic vitamin D2 therapy were treated for six to 12 months with oral 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) to determine its therapeutic effectiveness in vitamin D2-unresponsive osteodystrophy. On bone biopsy, three of the patients had severe osteomalacia and three showed predominant osteitis fibrosa. Previous therapies, including phosphate binders and dialysis schedules, were maintained. The three patients with osteomalacia and the two with osteitis fibrosa showed clinical deterioration. There was no significant change in serum calcium, phosphate, alkaline phosphatase, bone densitometry, immunoreactive parathyroid hormone levels or bone histology. Roentgenograms showed multiple new fractures of ribs and femoral necks in the patients with osteomalacia and increased bone resorption in two of three patients with osteitis fibrosa. 1,25-(OH)2D3 dosage had to be decreased in all patients because of hypercalcemia with a mean tolerated dose of 0.22 microgram/day. In these patients, 1,25-(OH)2D3 was not effective therapy for progressive osteodystrophy unresponsive to pharmacologic vitamin D2.

Familial renal hypophosphatemia, minor facial anomalies, intracerebral calcifications, and non-rachitic bone changes: apparently new syndrome?

We report on two brothers with renal hypophosphatemia, intracerebral calcifications, minor facial anomalies, and short distal phalanges. The children presented with recurrent dental abscesses; one had premature closure of the anterior fontanelle. Biochemical findings included hypophosphatemia and elevated serum alkaline phosphatase with normocalcemia. Blood levels of parathyroid hormone, 1,25(OH)2 and 25(OH) vitamin D levels were normal; TRP (the fractional tubular reabsorption of PO4) and TmP/GFR (the tubular maximum rate of PO4 reabsorption in relation to GFR) were low. Both parents had a normal serum phosphate and brain CT scan without evidence of calcifications. This apparently new syndrome of renal hypophosphatemia associated with intracerebral calcifications appears to be inherited as either an autosomal recessive or an X-linked trait.

Peritoneal dialysis in children after cardiopulmonary bypass.

OBJECTIVE: We reviewed 5 years' experience with peritoneal dialysis in children with acute renal failure after cardiac operations. We hypothesized that peritoneal dialysis is safe and effective in children with low-output cardiac failure after cardiac operations. RESULTS: Mortality in these patients with renal failure (n = 32) was 46.9%. Fluid removed by peritoneal dialysis was 48 +/- 28 ml/kg per 24 hours. Most complications of peritoneal dialysis were minor, hyperglycemia being the most frequent (53.1%). Peritoneal infection was suspected in 25%. Bowel perforation developed in two patients. None of the complications required early termination of dialysis. Hemodynamics and pulmonary function improved continuously during the study period. CONCLUSION: The early institution of peritoneal dialysis in acute renal failure and low cardiac output after cardiac operations not only removes fluid, thus easing fluid restriction, but may also improve cardiopulmonary function.

Urinary tract infections in the newborn: diagnosis from mid-stream urine specimens.

Mid-stream urines can be obtained for culture in the majority of neonates with a minimum of effort. Urines collected in plastic bags for cultures showed more than 10,000 organisms per ml. in over 50% of the specimens so obtained from healthy neonates. The use of bags or similar collecting devices should be discouraged. The use of skin disinfectants before obtaining the urine did not decrease the number of contaminants. A good mid-stream urine is more important in avoiding contamination than is the cleansing of the external genitals. Suprapubic aspiration or catheterization should be reserved for those infants in whom (a) repeat mid-stream urine cultures yield equivocal results and (b) the clinical situation does not allow time for repetition of a mid-stream urine culture.

Familial juvenile nephronophthisis. Experience with eleven cases.

Familial juvenile nephronophthisis (FJN) has an incidence in British Columbia of 1 per 50000 live births which gives a heterozygote frequency of 1 per 115. The authors report six families with a total of 11 cases. Multiple affected sibs are described in three families and in no instance was the condition present in more than one generation. The inheritance pattern is consistant with an autosomal recessive trait. The characteristic features are polyuria and azotemia though the presenting features may be either anemia or growth retardation with polyuria being elicited in the functional inquiry. There is a very hypotonic urine and absence of urinary sediment. Decreasing renal function at a variable rate is the fate of these patients, three of whom have had cadaver transplants.

Single-center experience with mycophenolate mofetil in pediatric renal transplant recipients.

Mycophenolate mofetil (MMF), a potent and specific inhibitor of guanosine nucleotide synthesis, is a new immunosuppressive drug used to prevent rejection in transplant patients. Extensive data on its utility and efficacy exists in adult patients but there is limited experience in pediatrics. Twenty-four children (14 male, 10 female; 2-19 yr of age), eight of whom had received living-related donor (LRD) transplants and 16 of whom had received cadaveric donor (CD) transplants, have been treated with MMF in our institution since September 1996. MMF was administered for a duration ranging from 13 weeks to 38 months, at an average dose of 600 mg/m2 (range: 200-1,000 mg/dose) every 12 h, for a total experience of 304 patient months. MMF capsules were used in 16 patients and/or pediatric suspension in eight. Five patients were switched to MMF from azathioprine as a result of rejection episodes or inability to taper prednisone, between 5 weeks and 3.5 yr post-transplant. All patients received prednisone, cyclosporin A (CsA), and induction therapy with anti-lymphocyte globulin (19 patients), anti-thymocyte globulin (one patient) or daclizumab (four patients). In 12 patients started on MMF at the time of CD transplant, five (42%) had an acute rejection episode. In seven who received a LRD transplant, one (14%) had an acute rejection episode. No patients who were converted to MMF were treated for acute rejection following conversion to MMF. One LRD graft was lost at 19 days following injury to the donor artery at the time of retrieval. At the last follow-up, the average creatinine level was 93 micromol/L and average urea level was 8.6 mmol/L. One patient developed epigastric distress. Three patients developed diarrhea/abdominal pain requiring dose adjustment. Five episodes of leukopenia and one episode of thrombocytopenia required dose adjustment. Two patients developed symptomatic cytomegalovirus (CMV) infection, one while on acyclovir prophylaxis. No malignancy has been encountered to date. Hence, MMF can be administered safely to children with good effect and with an acceptable side-effect profile.

Hypocalcemia and hypomagnesemia after ibuprofen overdose.

OBJECTIVE: To report a case of hypocalcemia and hypomagnesemia after ibuprofen overdose. CASE SUMMARY: A 21-month-old boy developed acute renal failure with severe metabolic acidosis after ingestion of ibuprofen 8 g. The infant developed tonic-clonic seizures 46 hours after ingestion, with significant hypocalcemia and hypomagnesemia that required electrolyte replacement to control the seizures. DISCUSSION: To our knowledge this is the first case report of hypocalcemia, hypomagnesemia, and seizures in a patient after ibuprofen overdose. The mechanism is unclear, the situation was probably aggravated by the use of sodium polystyrene sulfonate and furosemide. CONCLUSIONS: In patients with ibuprofen overdose, serum calcium and magnesium concentrations should be evaluated since seizures may be associated with a deficiency of these cations. The management of these patients should include calcium and/or magnesium supplementation when required and furosemide should be avoided.

Recurrent urinary tract infections in children.

Urinary tract infections are common in children and present in various ways. Diagnosis is based on findings of pyuria and bacteriuria. Management includes adequate and timely investigation, appropriate antibiotics, treatment of underlying contributing factors, and follow-up advice.

Childhood IgM nephropathy: comparison with minimal change disease.

The distinctiveness of IgM nephropathy (IgMN) as a clinicopathologic entity is controversial. Twenty-seven children (16 males, 11 females) with IgMN as defined immunohistochemically by diffuse mesangial staining of glomeruli for IgM were compared to a group of 63 children (40 males, 23 females) with minimal change disease (MCD). While mesangial expansion was significantly greater in IgMN than in MCD (p = 0.0014), there were no significant differences between the two groups with respect to the other biopsy factors. IgMN showed a significantly higher incidence of hypertension at presentation. More than 90% of patients in both groups presented with the nephrotic syndrome which in most initially responded to prednisone. Frequently relapsing/steroid-dependent nephrotic syndrome was the most common indication for biopsy in both groups. Approximately 60% of patients from both groups received cytotoxic therapy. Eight percent of IgMN and 7% of MCD patients failed to respond to therapy. Relapse rates and mean dose of prednisone at relapse were very similar in both groups prior to biopsy. Relapse rates diminished significantly after treatment in the postbiopsy interval, but mean dose of prednisone at relapse did not change appreciably over time. None of the patients developed renal failure or hypertension in the follow-up period. At last visit 23% of IgMN and 27% of MCD had proteinuria. The results indicate that IgMN and MCD are indistinguishable clinically in children who are biopsied for the nephrotic syndrome.

Megalourethra.

We present 5 examples of megalourethra. All 5 cases were associated with the spectrum of the triad syndrome, ranging from minor hydronephrosis and undescended testis to gross hydronephrosis incompatible with survival. Initial management of this urethral defect is drainage followed later by reconstruction.

Renal papillary necrosis in children with chronic arthritis.

Five ambulatory children with various types of chronic arthritis developed renal papillary necrosis (RPN), as documented by intravenous pyelography. Each child was being treated with nonsteroidal anti-inflammatory drugs (NSAIDs) at the time of diagnosis of RPN and had had episodes of gross or microscopic hematuria for several months prior to diagnosis. In each child hematuria was associated with more than one NSAID, and three of the five children also had ingested acetaminophen intermittently. Glomerular function has remained normal and hypertension has not developed, but management of these children has necessitated reduction or elimination of NSAIDs. As evidenced by these five cases, microscopic or gross hematuria in a child with chronic arthritis treated with anti-inflammatory drugs should raise the possibility of RPN.

Spurious rise in total carbon dioxide and chloride with negative anion gap after cystogram.

We report a case of spurious hyperchloraemia, elevated total carbon dioxide and negative anion gap 9 days following a voiding cystourethrogram (VCU) in a patient with bladder exstrophy and obstructive uropathy. We believe that the spurious laboratory results were due to analytical interference of the absorbed iodine with the method of bicarbonate and chloride measurement. The absorbed iodine was retained in the circulation for an extended period because of associated renal impairment. Our patient was also on piperacillin which might have interfered with iodine clearance. Physicians and laboratory pathologists should be aware of this effect when interpreting laboratory results of patients who have undergone a VCU in association with obstructive uropathy and impaired renal function.

Prognostic factors in diffuse proliferative lupus glomerulonephritis.

A number of clinical laboratory and biopsy-derived parameters were assessed for their prognostic significance in the short (24 months), intermediate (60 months) and long terms in 45 patients (43 female, 2 male) with diffuse proliferative lupus glomerulonephritis (DPGN). The factors evaluated were serum creatinine (SCr) and urinary protein at time of biopsy, initial dose of prednisone and immunosuppressive after biopsy, activity index (AI), chronicity index (CI), their individual components, extent of extraglomerular (tubulo-interstitial) immune deposits (EGD) and mean number of intraglomerular monocytes per glomerulus (NSE index). Using proportional hazards analysis to evaluate the parameters, SCr (P = 0.003), AI (P = 0.005) and NSE index (P = 0.038) were shown to be significant predictors of outcome when all variables except the components of AI and CI were considered. When AI and CI were omitted but their components included, SCr (P = 0.0005), NSE index (P = 0.024), extent of karyorrhexis (P = 0.035) and glomerulosclerosis (P = 0.033) were then demonstrated to be significant prognostic factors of DPGN. The results suggest that intraglomerular monocyte infiltration has a protective effect and confirm that AI index is a relatively powerful predictor of outcome. Histologic and nonhistologic biopsy factors contribute significant additional prognostic information to that provided by SCr.

Deregulation of cell survival in cystic and dysplastic renal development.

Various aberrations of cell biology have been reported in polycystic kidney diseases and in cystic renal dysplasias. A common theme in these disorders is failure of maturation of renal cells which superficially resemble embryonic tissue. Apoptosis is a feature of normal murine nephrogenesis, where it has been implicated in morphogenesis, and fulminant apoptosis occurs in the small, cystic kidneys which develop in mice with null mutations of bcl-2. Therefore, we examined the location and extent of apoptosis in pre- and postnatal samples of human polycystic and dysplastic kidney diseases using propidium iodide staining, in situ end-labeling and electron microscopy. In dysplastic kidneys cell death was prominent in undifferentiated cells around dysplastic tubules and was occasionally found in cystic epithelia. The incidence of apoptosis was significantly greater than in normal controls of comparable age both pre- and postnatally. In the polycystic kidneys there was widespread apoptosis in the interstitium around undilated tubules distant from cysts, in undilated tubules between cysts and in cystic epithelia. The level of apoptosis compared to controls was significantly increased postnatally. A similar increase of cell death was also noted in the early and late stages of renal disease in the polycystic cpk/cpk mouse model. We speculate that deregulation of cell survival in these kidneys may reflect incomplete tissue maturation, and may contribute to the progressive destruction of functional kidney tissue in polycystic kidneys and the spontaneous involution reported in cystic dysplastic kidneys.