oxalates and Hyperplasia

Acquired cystic disease (ACD) is a recently described phenomenon occurring in the native kidneys of patients treated with long-term dialysis. Renal cell carcinoma is being diagnosed with increasing frequency in patients with chronic renal failure. In most, but not all, instances the cancers develop in association with ACD. Careful microscopic examination of end-stage kidneys undergoing dialysis discloses cysts lined with hyperplastic cells. Papillary hyperplasia of cyst epithelium is recorded in virtually every detailed pathology report of tumors arising in ACD and is the likely pathogenetic basis for the development of renal tumors in cystic kidneys undergoing dialysis. The pathology of ACD and its related neoplasms is reviewed. An estimate is made of the incidence of ACD and renal cell carcinoma in patients receiving dialysis by tabulating data from studies published in medical journals. Acquired cystic disease is found in approximately 35% of patients treated by long-term hemodialysis. Renal cell carcinoma occurs in approximately 5.8% of cases of ACD. Most of the cancers are found incidentally at autopsy or by examination of kidneys from bilateral nephrectomies and are of little clinical significance, but occasional cases present aggressive neoplasms that metastasize and cause the deaths of patients.

Topics: Age Factors; Carcinoma, Renal Cell; Epithelium; Female; Humans; Hyperplasia; Kidney Failure, Chronic; Kidney Neoplasms; Male; Oxalates; Polycystic Kidney Diseases; Renal Dialysis; Time Factors

In patients with primary hyperoxaluria (PH), endogenous oxalate overproduction increases urinary oxalate excretion, leading to compromised kidney function and often kidney failure. Highly elevated plasma oxalate (Pox) is associated with systemic oxalate deposition in patients with PH and severe chronic kidney disease (CKD). The relationship between Pox and estimated glomerular filtration rate (eGFR) in patients with preserved kidney function, however, is not well established. Our analysis aimed to investigate a potential correlation between these parameters in PH patients from three randomized, placebo-controlled trials (studies OC3-DB-01, OC3-DB-02, and OC5-DB-01).. Baseline data from patients with a PH diagnosis (type 1, 2, or 3) and eGFR > 40 mL/min/1.73 m. A total of 106 patients were analyzed. A statistically significant inverse Spearman's correlation between eGFR and Pox was observed across all analyses; correlation coefficients were - 0.44 in study OC3-DB-01, - 0.55 in study OC3-DB-02, - 0.51 in study OC5-DB-01, and - 0.49 in the pooled studies (p < 0.0064).. Baseline evaluations showed a moderate and statistically significant inverse correlation between eGFR and Pox in patients with PH already at early stages of CKD (stages 1-3b), demonstrating that a correlation is present before substantial loss in kidney function occurs.

Topics: Glomerular Filtration Rate; Humans; Hyperoxaluria, Primary; Hyperplasia; Kidney; Oxalates; Renal Insufficiency, Chronic

Muraglitazar, a PPARalpha/gamma dual agonist, was dosed orally to rats once daily for 13 weeks to evaluate urinary and urothelial changes of potential relevance to urinary bladder tumorigenesis. Groups of 17 young or aged rats per sex were fed a normal or 1% NH4Cl-supplemented diet and were dosed with 0, 1, or 50 mg/kg muraglitazar. Lithogenic ions and sediment were profiled from freshly voided urine samples collected 24 h after dosing, and drug exposures were measured. Urinary citrate, oxalate, and epidermal growth factor (EGF) were assayed from 18-h urine collections. Urothelium was assessed by light microscopy, scanning electron microscopy, and BrdU and TUNEL immunohistochemistry. When fed a normal diet, urine pH was higher in males (above 6.5). Urine volume/body weight was greater in females. Urine soluble/total calcium and magnesium and phosphorus/creatinine ratios were lower in male rats fed a normal diet. Urine citrate levels were decreased and oxalate was increased in young male rats treated with 50 mg/kg muraglitazar compared to age/sex/diet-matched controls. No changes in urine sediment were detected 24 h after dosing. In young male rats treated with 50 mg/kg on normal diet, multifocal urothelial necrosis and proliferation were observed, whereas urothelial apoptosis and urine EGF levels were unchanged compared to age/sex/diet-matched controls. Urothelial necrosis and proliferation were not correlated to systemic or urinary drug exposures and were prevented by dietary acidification. These data suggest that muraglitazar-associated changes in urine composition predispose to urothelial cytotoxicity and proliferation in the urinary bladder of young male rats and that urine sediment must be profiled at multiple daily timepoints to fully qualify drug-induced changes in urine composition.

Topics: Age Factors; Animals; Apoptosis; Calcium; Cell Proliferation; Citrates; Creatinine; Dose-Response Relationship, Drug; Epidermal Growth Factor; Female; Glycine; Hyperplasia; Magnesium; Male; Oxalates; Oxazoles; Peroxisome Proliferators; Phosphorus; PPAR alpha; PPAR gamma; Rats; Rats, Sprague-Dawley; Sex Factors; Time Factors; Urinary Bladder; Urine; Urothelium

Kidneys removed from 58 pediatric patients at renal transplantation (except 3 cases), who had developed chronic renal failure and were maintained on dialysis, were investigated histopathologically, and the clinical profiles were taken into account. The patients ranged in age from 2 to 24 years, with an average of 11.2 years. The duration of dialysis ranged from 0.5 to 63 months, with an average of 12.6 months. The kidneys, which were conventionally prepared for histological observation, were subjectively divided into three groups depending on the degree of remaining nephrons. Patients with completely atrophic type (type 1), incompletely atrophic type (type 2), and mixed type of atrophy and hypertrophy (type 3) had a duration of dialysis of 20.0, 12.3, 6.3 months, respectively (Type 1 greater than Type 3, P less than 0.01). A correlation between histology and function was demonstrated, since urinary output was more than 200 ml/day in most of the type 3 patients, and less than 20 ml/day in all of the patients with type 1. The findings suggest that the functioning nephrons that remained at the beginning of dialysis generally become atrophic within one year after the initiation of dialysis. The ratio of kidney weight to body weight showed a significant negative correlation with both the duration of dialysis and that of illness. The histopathological changes seen in kidneys of patients on dialysis were reviewed. The findings suggested that certain changes, unusual epithelial proliferations an oxalate deposition, are associated with persisting renal function rather than the duration of dialysis.

Topics: Adolescent; Adult; Body Weight; Cell Division; Child; Child, Preschool; Female; Humans; Hyperplasia; Kidney; Kidney Failure, Chronic; Male; Organ Size; Oxalates; Oxalic Acid; Renal Dialysis; Time Factors; Urination