Glomerular podocyte dysfunction in inherited renal tubular disease

Background Hereditary renal tubular disease can cause hypercalciuria, acid-base imbalance, hypokalemia, hypomagnesemia, rickets, kidney stones, etc. If these diseases are not diagnosed or treated in time, they can cause kidney damage and electrolyte disturbances, which can be detrimental to the maturation and development of the child. Glomerular involvement in renal tubular disease patients has only been considered recently. Methods We screened 71 papers (including experimental research, clinical research, etc.) about Dent’s disease, Gitelman syndrome, and cystinosis from PubMed, and made reference. Results Glomerular disease was initially underestimated among the clinical signs of renal tubular disease or was treated merely as a consequence of the tubular damage. Renal tubular diseases affect glomerular podocytes through certain mechanisms resulting in functional damage, morphological changes, and glomerular lesions. Conclusions This article focuses on the progress of changes in glomerular podocyte function in Dent disease, Gitelman syndrome, and cystinosis for the purposes of facilitating clinically accurate diagnosis and scientific treatment and improving prognosis.

Gitelman Syndrome: A Rare Cause of Persistent Hypokalemia

Gitelman syndrome is a rare autosomal recessive renal tubular disease, caused by mutations in the SLC12A3 gene, which encodes the renal thiazide-sensitive sodium-chloride cotransporter (NCCT) in the distal renal convoluted tubule. We present a 48-years-old male referred to our observation after being considered not suitable to a previous proposed surgery due to persistent hypokalemia. No valued symptoms were described. Laboratory tests showed metabolic alkalosis, hypomagnesemia, hypokalemia and secondary hyperaldosteronism. Genetic test was performed and sequence analysis of the SLC12A3 gene revealed a homozygous mutation confirming this disease. The aim of this report is to remind and increase awareness of the existence of GS, manage the condition properly and consider the risk of disease recurrence to the next generations.

Excretion of beta 2-glycoprotein I (apolipoprotein H) in renal tubular disease

beta 2-Glycoprotein I (beta 2GI) was identified as a major urinary protein excreted by patients with several renal tubular diseases, including adult Fanconi syndrome, nephrocalcinosis associated with autoimmune diseases, Lowe's syndrome, and Dent's disease (a familial renal tubular disease). Sixteen patients excreted between 2 and 40 mg of beta 2GI per millimole of creatinine. In contrast, 18 healthy controls had undetectable amounts of beta 2GI in urine. Isoelectric focusing followed by immunoblotting demonstrated multiple forms of beta 2GI with pls between 6.4 and 8.2. These pls are higher than for several other "tubular proteins"; beta 2GI may therefore be less retarded than more-anionic proteins by the glomerular charge-barrier. This could explain why large quantities of beta 2GI are excreted despite its relatively high molecular mass (50 kDa). Excretion of beta 2GI was easily demonstrated by routine electrophoresis of urine proteins. beta 2GI migrates in the beta-gamma region and may be confused with Bence Jones protein. beta 2GI is stable for at least two years in urine frozen at -25 degrees C.