Tubulopathy in nephrolithiasis: Consequence rather than cause

Abstract

To address whether a renal tubular dysfunction is encountered in a particular patient subgroup with urolithiasis, the following parameters of tubular function were measured in urine taken in the morning from 214 stone formers after fasting: pH, excretion of lysozyme and gamma-glutamyl transferase (gamma-GT); fractional excretion (FE) of glucose, insulin, Mg, K, and HCO3 after an alkali loading; and the renal threshold for phosphate (TmP/GFR). The following diagnoses were made in the patient group: primary hyperparathyroidism (N = 8), medullary sponge kidneys (N = 21), hyperuricemia (N = 10), cystinuria (N = 2), struvite stone disease (N = 6), idiopathic hypercalciuria of the absorptive (N = 25), dietary (N = 69) or renal (N = 7) type, and normocalciuric idiopathic urolithiasis (N = 66). In 31% of the patients TmP/GFR was below 0.80 mmole/liter and in 13% of the patients, FE HCO3 after alkali loading was above normal. Urinary excretion of lysozyme and that of gamma-GT both were elevated in 17% of the patients. FE glucose, FE insulin, FE Mg, and FE K were elevated in 8, 9, 3, and 7% of the patients, respectively. This study demonstrates that a significant number of stone formers present with signs of renal tubular dysfunction, primarily involving the proximal tubule since apparent leaks of phosphate and of bicarbonate were most frequently encountered. The defects were not specific for a given etiologic group of patients; on the other hand, occurrence was related to the presence of large stones in the pyelocaliceal system at the time data were gathered. Taken together these data suggest that the tubulopathy in nephrolithiasis is the consequence rather than the cause of the stone.

Effects of Extracorporeal Shock Wave Lithotripsy on Renal Function in Patients with Kidney Stone Disease

“…Schardijn et al [14] and Musialik [15], who analyzed urinary β 2 m excretion, found that β 2 m values are similar in healthy people and in patients with active metabolic stone disease without UTI symptoms, whereas in patients with active metabolic stone disease and UTI, the excretion of β 2 m in the urine was 20-fold higher than in healthy subjects. This confirms the previous results of Jaeger et al [16] who suggested that in patients with nephrolithiasis a proximal tubule defect may be the result of an infectious process which is commonly related to the presence of stones in the kidney. An increased β 2 m excretion has been reported in patients with renovascular hypertension, in patients under hemodialysis or after renal transplantation, as well as in patients with UTI [12, 14, 15, 17].…”

Modulation of Proliferating Renal Epithelial Cell Affinity for Calcium Oxalate Monohydrate Crystals

“…Increased excretion of cellular enzymes has been observed in the urine of stoneforming humans (18,19) and of oxalate-loaded rats (20), and it has been postulated that cellular damage could result from crystal deposition. However, when the nephrotoxin gentamycin was administered to rats together with oxalate, crystal deposition was enhanced (31), suggesting that cellular damage might precede and promote crystal retention, rather than be a consequence of the crystals.…”

“…In addition, studies in stoneforming humans (18,19) and oxalate-loaded rats (20) have demonstrated that renal cellular injury occurs. In the current study, we defined the effect of diverse injuries to renal cells on crystal adhesion and how the PGE system might modulate this response.…”

Hyperoxaluria or hypercalciuria in nephrolithiasis: the importance of renal tubular functions

“…It has previously been ing stones [16][17][18][19][20]. Tubular dysfunctions can either be shown that tubular defects, expressed as incomplete a consequence of structural defects or caused by acidification disturbances and/or tubular proteinuria, hormonal or metabolic influence.…”