P < 0.001 (Fisher exact probability test).c l i n i c a l i n v e s t i g a t i o n AM _ Zurowska et al.: Mild Alport syndrome due to founder COL4A5 p.G624D AM _ Zurowska et al.: Mild Alport syndrome due to founder COL4A5 p.G624D c l i n i c a l i n v e s t i g a t i o n Kidney International (2021) -, ---AM _ Zurowska et al.: Mild Alport syndrome due to founder COL4A5 p.G624Dc l i n i c a l i n v e s t i g a t i o n

Tubulointerstitial fibrosis and tubular atrophy play a crucial role in the pathogenesis of chronic kidney disease (CKD). They are also major determinants in chronic kidney disease development and progression in patients with primary renal diseases characterized by persistent or recurrent proteinuria. The purpose of the study was to assess urinary excretion of alpha-glutathione S-transferase (alpha-GST), pi-glutathione S-transferase (pi-GST), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and serum NGAL level in children with idiopathic nephrotic syndrome (INS). Patients and methods: the study group comprised of 39 children with INS and the control group consisted of 20 healthy children. A total of 23 patients were affected with steroid-dependent nephrotic syndrome (SDNS) and 16 with steroid-resistant nephrotic syndrome (SRNS). In the majority of patients, a histopathologic examination revealed minimal change disease (MCD)—25 (64%). Focal segmental glomerulosclerosis (FSGS), mesangioproliferative glomerulonephritis (MesPGN), membranoproliferative glomerulonephritis (MPGN), and membranous glomerulonephritis (MGN) were diagnosed in 4 (10.3 %), 6 (15.5%), 2 (5.1%), and 2 (5.1%) children, respectively. Urinary alpha-GST, urinary pi-GST, urinary KIM-1, and urinary and serum NGAL concentrations were measured using specific enzyme-linked immunosorbent assay. The urinary results were expressed in nanograms per milligram of creatinine (ng/mg). Results: The authors observed significantly higher levels of urinary alpha-GST/creatinine ratio (P = 0.03), urinary KIM-1/creatinine ratio (P < 0.02), serum NGAL level (P < 0.01), and urinary NGAL/creatinine ratio (P = 0.02) in children with INS compared with controls. The median values of urinary pi-GST/creatinine ratio in children with INS and controls did not differ significantly. In children with SRNS, the median values of urinary NGAL/creatinine ratio (P = 0.02) and urinary KIM-1/creatinine ratio (P = 0.02) were significantly higher compared with children with SDNS. The authors noted significant positive correlation between KIM-1/creatinine ratio and proteinuria (r = 0.56, P < 0.05). The analysis of alpha-GST/creatinine ratio, pi-GST/creatinine ratio, sNGAL, and uNGAL/creatinine ratio concerning the histopathologic examination, the duration of the disease, and number of relapses did not show any significant differences. Conclusions: 1. Both children with SDNS and those with SRNS were characterized by increased tubular injury marker levels. 2. Patients with SRNS and higher proteinuria are more susceptible to early kidney damage.

Wrodzona biegunka chlorowa (CCD -congenital chloride diarrhea) to rzadka choroba o dziedziczeniu autosomalnym recesywnym. Jej podłożem są mutacje genu SLC26A3 kodującego wymiennik jonów Cl -/HCO 3 -, umiejscowiony w szczytowej błonie nabłonka jelita krętego i okrężnicy. Skutkiem jest upośledzona absorpcja chlorków i sekrecja wodorowęglanów, co manifestuje się wodnistą biegunką o wysokiej zawartości jonów chlorkowych. Typowo choroba objawia się już prenatalnie pod postacią wielowodzia, obecności rozdętych pętli jelitowych płodu i często skutkuje porodem przedwczesnym. Od urodzenia obserwuje się wodnistą biegunkę, nawracające wymioty, opóźniony rozwój fizyczny, a w badaniach laboratoryjnych hipochloremiczną alkalozę metaboliczną, hipokaliemię i hiponatremię. Przedstawiamy przypadek obecnie 8-letniej dziewczynki, z biegunką chlorową traktowaną do 5 r.ż. jako zespół Barttera. Nieprawidłowe rozpoznanie wynikało z klinicznych i biochemicznych podobieństw obu jednostek chorobowych i późnym, związanym z używaniem pampersów, rozpoznaniem przewlekłej biegunki. Ostatecznym potwierdzeniem CCD było badanie genetyczne, które ujawniło obecność mutacji genu SLC26A3 (p.IIe(TCA)657dup). Zastosowanie celowanego leczenia pozwoliło na znaczące złagodzenie skutków choroby i umożliwiło prawidłowy rozwój dziecka. Przedstawiony przypadek wskazuje na potencjalne trudności związane z diagnostyką różnicową zespołu Barttera i jest dowodem na korzyści płynące z dostępu do badań molekularnych. S Ł O W A K L U C Z O W Ewrodzona biegunka chlorowa, zespół Barttera, hipochloremiczna alkaloza metaboliczna

Rationale: Medullary sponge kidney (MSK) is a rare congenital abnormality characterized by cystic dilatation of the medullary collecting tubules. The disorder is likely to be complicated by nephrocalcinosis, urolithiasis, tubular dysfunctions, and urinary tract infections. In addition, it may be rarely associated with extrarenal anomalies. Patient concern: We present a case of 17-year old girl who was referred for metabolic evaluation of bilateral nephrocalcinosis. Physical examination showed signs of mild, left-sided hemihypertrophy involving the lower limb, buttock, trunk, face, and tongue. The imaging studies of kidneys including intravenous urography and contrast computed tomography showed numerous medullary calcification and a typical picture of MSK—“paint brush”/“bouquet of flowers” appearance of the dilated tubules within the renal medulla. Laboratory evaluation revealed sterile pyuria, hypercalciuria, and hypocitraturia. Intervention: The patient was subsequently treated with potassium citrate, hydrochlorothiazide, low sodium and low oxalate diet accompanied by high fluid intake. Outcomes: After a 1-year therapy the normalization of calciuria and citraturia occurred and no progression of nephrocalcinosis was observed. Lessons: We conclude that MSK should always be considered as a cause of nephrocalcinosis. Since the final diagnosis requires specific imaging techniques, the concomitant extrarenal abnormalities such as hemihypertrophy may facilitate diagnostic decisions.