Kidney stones and moderate proteinuria as the rare manifestations of Gitelman syndrome

Abstract

Background Gitelman syndrome (GS) is an autosomal recessive inherited salt-losing tubulopathy (SLT). Here, we describe, for the first time, a case of GS without Gitelman-like features and with concomitant kidney stones, cysts and diabetic nephropathy (DN). Case presentation We described a male patient had a 19-year history of recurrent fatigue. From childhood, he had polydipsia and polyuria, paroxysmal tetany and palpitation. Serum biochemistry revealed chronic hypokalemia, metabolic alkalosis, normomagnesemia, mildly elevated Cr. Concomitant 24 h urine collection showed inappropriate renal potassium wasting, borderline hypercalciuria, moderate proteinuria consisting of major glomerular. Ultrasound of urinary tract showed bilateral and multiple kidney stones and cysts. Whole exome sequencing (WES) identified compound heterozygous mutations of SLC12A3. The unusual association of SLTs and glomerular proteinuria prompted us to perform a renal biopsy. Renal pathology showed renal involvement consistent with GS and early stage of diabetic nephropathy (DN). After treatment with KCl, magnesium oxide, perindopril and acarbose, the patient had been cured. The fatigue didn’t relapse. Conclusion GS had high variability of phenotype, GS may have no Gitelman-like features, kidney stones are not the exclusion criteria of GS. Renal biopsy should be warranted for GS patients with moderate to massive glomerular proteinuria.

Rapidly Progressing to ESRD in an Individual with Coexisting ADPKD and Masked Klinefelter and Gitelman Syndromes

“…However, we have not found electrolyte alterations characteristic of GS in our proband. Thus, the phenotypic effect of such missense variants is difficult to evaluate, and some pathogenic variants may not be sufficient to cause phenotypic changes related to GS [ 27 , 28 , 29 , 30 , 31 ], although, we cannot rule out that modifier genes are involved in the onset of GS or that phenotypic changes caused by this compound heterozygous would be apparent later in life. Indeed, our proband had a reduced eGFR at the time of the first evaluation, and this fact could in part mask the electrolyte alterations of GS ( Table 1 ).…”

“…GS is clinically characterized by hypomagnesemia, hypochloremic metabolic alkalosis, hypokalemia, hypereninemia, and hyperaldosteronism with normal or low blood pressure and salt loss [ 27 ]. Most of patients with GS present during childhood or early adulthood, however, it has high clinical variability, and some patients may not have GS features [ 27 , 28 , 29 , 30 , 31 ]. We here report a patient with ADPKD and coexisting masked KS and GS, based on genetic studies and clinical features.…”

A case of Gitelman syndrome with membranous nephropathy

“…However, nephrotic-range glomerular proteinuria in GS patients is rare generally. At present, there are 6 cases of GS accompanied by moderate to nephrotic-range proteinuria [ 12 – 17 ]. Two of the patients were female and four were male; Three patients presented with nephrotic syndrome, two of whom received glucocorticoid therapy; 5 patients underwent renal biopsy, including C1q nephropathy, minimal change disease (MCD), diabetic nephropathy and 2 cases of focal segmental glomerulosclerosis (FSGS) (Table 2 ).…”

“…Therefore, renal biopsy should be warranted for GS patients with moderate to nephrotic-range glomerular proteinuria. If there are primary glomerular diseases, glucocorticoid or other drugs may be added, in addition to potassium and magnesium supplements for GS [ 12 , 17 ].…”

Molecular Basis, Diagnostic Challenges and Therapeutic Approaches of Bartter and Gitelman Syndromes: A Primer for Clinicians

“…It would be interesting to expand these clinical case studies, paying particular attention to the interactions between NKCC2 and CASR (extracellular calcium-sensing receptor) (the molecular target of drugs for hyperparathyroidism) [ 82 ]. Recent studies have suggested that GS [ 83 , 84 , 85 ] and BS [ 34 , 85 , 86 ] may be associated with glomerular damage, despite being classic tubulopathies. In both cases, moderate proteinuria associated with focal lesions of segmental glomerular sclerosis and thickening of the glomerular basement membrane have been reported [ 84 ].…”