Liver transplantation in oxalosis prior to advanced chronic kidney disease.

While curative of the disease, combined kidney and liver transplantation (K/LTx) for primary hyperoxaluria type 1 (PH1) continues to carry with it a risk for patient death of 15-25%, which over time may not differ from that of kidney transplantation alone (KTx). In this editorial, survival data are reviewed as well as the limited data available for kidney graft function, which may favor K/LTx in the short term but is more uncertain in the longer term. The window of opportunity that favors preemptive K/LTx is relatively narrow and is likely even narrower for preemptive isolated LTx. Capability and experience in the medical management of such patients, and the opportunities available, as well as likely patient compliance, so far without supporting data, may be the most important determination of the best strategy for management.

Sickle cell disease and the kidney.

The renal features of sickle cell disease (SCD) include some of the most common reasons for referral to nephrologists, such as hematuria, proteinuria, tubular disturbances and chronic kidney disease. Therapy of these conditions requires specialized knowledge of their distinct pathogenic mechanisms. Painless hematuria is usually benign--unless massive--and can be treated with hydration alone if renal medullary carcinoma has been ruled out. Tubular functional defects, which tend to reduce urinary concentrating capacity, generally require no specific treatment. Proteinuria might indicate the development of chronic sickle cell nephropathy, which can be treated effectively. Measurement of glomerular filtration rate in SCD is problematic, which makes identification and monitoring of chronic kidney disease difficult in patients with SCD. Although managing and predicting the outcomes of chronic kidney disease in the SCD setting is challenging, affected individuals do benefit from transplantation. This Review summarizes the presentation, processes, pathology, modifiers, diagnosis and treatment of the renal effects of SCD.

Pyridoxamine lowers oxalate excretion and kidney crystals in experimental hyperoxaluria: a potential therapy for primary hyperoxaluria.

In order to prevent kidney stones and nephrolithiasis in hyperoxaluria, a new treatment that specifically reduces oxalate production and therefore urinary oxalate excretion would be extremely valuable. Pyridoxamine(PM) could react with the carbonyl intermediates of oxalate biosynthesis, glycolaldehyde and glyoxylate, and prevent their metabolism to oxalate. In PM treated rats, endogenous urinary oxalate levels were consistently lower and became statistically different from controls after 12 days of experiment. In ethylene glycol-induced hyperoxaluria, PM treatment resulted in significantly lower (by ~50%) levels of urinary glycolate and oxalate excretion compared to untreated hyperoxaluric animals, as well as in a significant reduction in calcium oxalate crystal formation in papillary and medullary areas of the kidney. These results, coupled with favorable toxicity profiles of PM in humans, show promise for the therapeutic use of PM in primary hyperoxaluria and other kidney stone diseases.

Pyridoxamine lowers kidney crystals in experimental hyperoxaluria: a potential therapy for primary hyperoxaluria.

BACKGROUND: Primary hyperoxaluria is a rare genetic disorder of glyoxylate metabolism that results in overproduction of oxalate. The disease is characterized by severe calcium oxalate nephrolithiasis and nephrocalcinosis, resulting in end-stage renal disease (ESRD) early in life. Most patients eventually require dialysis and kidney transplantation, usually in combination with the replacement of the liver. Reduction of urinary oxalate levels can efficiently decrease calcium oxalate depositions; yet, no treatment is available that targets oxalate biosynthesis. In previous in vitro studies, we demonstrated that pyridoxamine can trap reactive carbonyl compounds, including intermediates of oxalate biosynthesis. METHODS: The effect of PM on urinary oxalate excretion and kidney crystal formation was determined using the ethylene glycol rat model of hyperoxaluria. Animals were given 0.75% to 0.8% ethylene glycol in drinking water to establish and maintain hyperoxaluria. After 2 weeks, pyridoxamine treatment (180 mg/day/kg body weight) started and continued for an additional 2 weeks. Urinary creatinine, glycolate, oxalate, and calcium were measured along with the microscopic analysis of kidney tissues for the presence of calcium oxalate crystals. RESULTS: Pyridoxamine treatment resulted in significantly lower (by approximately 50%) levels of urinary glycolate and oxalate excretion compared to untreated hyperoxaluric animals. This was accompanied by a significant reduction in calcium oxalate crystal formation in papillary and medullary areas of the kidney. CONCLUSION: These results, coupled with favorable toxicity profiles of pyridoxamine in humans, show promise for therapeutic use of pyridoxamine in primary hyperoxaluria and other kidney stone diseases.

Sickle cell disease and the kidney.

Sickle cell disease (SCD) affects the kidney by acute mechanisms, as a form of the sickle crisis, and insidiously with renal medullary/papillary necrosis, with resulting tubular defects. Glomerular hyperperfusion and hypertrophy results in a chronic sickle cell nephropathy that results in a significant morbidity in the progression to end-stage kidney disease. Kidney transplantation offers a major advantage to survival, and should be coupled with efforts toward prevention of recurrent disease.