Tubular Disorders Research Articles

Gitelman syndrome patient managed with amiloride during pregnancy and lactation

Gitelman Syndrome (GS) is a rare autosomal-recessive tubular disorder characterized by hypokalemia, hypomagnesemia, metabolic alkalosis, hyperreninemic hyperaldosteronism, and normotension. Management of GS during pregnancy is particularly challenging due to pregnancy-associated renal physiological changes and due to controversial safety profiles regarding teratogenicity of medications commonly used for GS management in non-pregnant patients. We report a case of a 20-year-old female patient diagnosed of GS who was treated with amiloride during pregnancy and lactation due to persistent hypokalemia resistant to oral supplementation therapy. Use of amiloride facilitated control of hypokalemia and hypomagnesemia in the mother without causing any noticeable side effects in the newborn.

4-Phenylbutyric Acid Treatment Reduces Low-Molecular-Weight Proteinuria in a Clcn5 Knock-in Mouse Model for Dent Disease-1.

Dent disease-1 (DD-1) is a rare X-linked tubular disorder characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrolithiasis and nephrocalcinosis. This disease is caused by inactivating mutations in the CLCN5 gene which encodes the voltage-gated ClC-5 chloride/proton antiporter. Currently, the treatment of DD-1 is only supportive and focused on delaying the progression of the disease. Here, we generated and characterized a Clcn5 knock-in mouse model that carries a pathogenic CLCN5 variant, c. 1566_1568delTGT; p.Val523del, which has been previously detected in several DD-1 unrelated patients, and presents the main clinical manifestations of DD-1 such as high levels of urinary b2-microglobulin, phosphate and calcium. Mutation p.Val523del causes partial ClC-5 retention in the endoplasmic reticulum. Additionally, we assessed the ability of sodium 4-phenylbutyrate, a small chemical chaperone, to ameliorate DD-1 symptoms in this mouse model. The proposed model would be of significant value in the investigation of the fundamental pathological processes underlying DD-1 and in the development of effective therapeutic strategies for this rare condition.

A novel heterozygous likely pathogenic SLC5A2 variant in a diabetic patient with glucosuria and aminoaciduria.

Familial renal glucosuria (FRG) is a rare renal tubular disorder characterized by increased urinary glucose excretion despite normoglycemia. It is most commonly caused by pathogenic variants in the solute carrier family V member 2 (SLC5A2) gene. This gene encodes the sodium-glucose cotransporter 2, crucial for glucose reabsorption. We report the case of a 44-year-old male referred to the endocrinology outpatient clinic for unexplained glucosuria despite well-controlled diabetes mellitus with metformin and gliclazide therapy. His main complaints were nocturia and an unintentional 5 kg weight loss in 1 year. A 24-h urinary collection revealed overt glucosuria (23.3 g/1.73 m2/24 h), generalized aminoaciduria, and increased uric acid excretion (fractional excretion: 6.4%). Whole-exome sequencing revealed a novel heterozygous c.469-1G>A likely pathogenic variant in the SLC5A2 gene. Specific analysis of the maturity-onset diabetes of the young type (MODY) gene panel showed no pathogenic variants in the hepatocyte nuclear factor-1A (HNF-1A; MODY3) nor in other MODY-associated genes. We assume that the association of glucosuria, aminoaciduria, and increased uric acid excretion can be explained by the combination of diabetes and the likely pathogenic SLC5A2 variant in this patient. In conclusion, we describe a well-controlled diabetic patient with FRG, associated with a novel heterozygous c.469-1G>A likely pathogenic variant in the SLC5A2 gene. The diagnosis of a renal tubular disorder should be considered in patients with unexplained glucosuria and diabetes mellitus, especially if the latter is well controlled. FRG usually presents with glucosuria but may be associated with generalized aminoaciduria and hyperuricosuria. Genetic analysis should be considered in patients with young-onset diabetes and glucosuria, particularly with a positive family history.

389-P: ChREBP-ß Aggravates Fructose-Induced Renal Tubular Reabsorption Disorder by Regulating Endoplasmic Reticulum Stress and Mitochondrial Dysfunction

389-P: ChREBP-ß Aggravates Fructose-Induced Renal Tubular Reabsorption Disorder by Regulating Endoplasmic Reticulum Stress and Mitochondrial Dysfunction

Effect of vitamin D in experimental varicocele model in rats

Purpose: Varicocele is a pathological condition that affects approximately 20% of adult men, causing infertility and sperm deterioration. The aim of our study was to investigate the efficacy of vitamin D (Vit. D) in the pathophysiology of varicocele. We performed biochemical, gene expression analyses and histopathological to evaluate the efficacy of vitamin D in the experimental varicocele model.
 Materials and Methods: In the study, 30 adult male Wistar Albino rats were used. The rats were divided into 3 groups equally as control group, experimental group (varicocele), treatment group (varicocele + D vit.). The treatment group received 500 IU/kg D vit. intramuscularly.
 Results: Histopathological, TRPM2-8 gene expression and biochemical analyses were performed on testicular and blood samples collected at the end of the experiment. The experimental group showed a deterioration in tubular structure, a decrease in total antioxidant levels and an increase in total oxidant levels. The treatment group, on the other hand, showed an increase in TAS, a decrease in TOS and a beneficial improvement in tubular structure disorders. Analysis of gene expression levels showed that TRPM2-8 expression levels were significantly increased in the varicocele group and decreased in the treatment group.
 Conclusion: In the varicocele model, the use of vitamin D had a significant effect on TRPM2-8 gene level, pathological seminiferous tubules and biochemical values. Further studies are needed to determine the clinical application of vitamin D in varicocele disease.

TAK-242 improves sepsis-associated acute kidney injury in rats by inhibiting the TLR4/NF-κB signaling pathway

Objective This study was designed to observe the effect of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway activity on sepsis-associated acute kidney injury (SA-AKI), thereby providing new considerations for the prevention and treatment of SA-AKI. Methods The rats were divided into Sham, cecal ligation and puncture (CLP), CLP + vehicle, and CLP + TAK-242 groups. Except the Sham group, a model of CLP-induced sepsis was established in other groups. After 24 h, the indicators related to kidney injury in blood samples were detected. The pathological changes in the kidneys were observed by hematoxylin-eosin staining, and tubular damage was scored. Oxidative stress-related factors, mitochondrial dysfunction-related indicators in each group were measured; the levels of inflammatory factors in serum and kidney tissue of rats were examined. Finally, the expression of proteins related to the TLR4/NF-κB signaling pathway was observed by western blot. Results Compared with the CLP + vehicle and CLP + TAK-242 groups, the CLP + TAK-242 group reduced blood urea nitrogen (BUN), creatinine (Cr), cystatin-C (Cys-C), reactive oxygen species (ROS), malondialdehyde (MDA), and inflammatory factors levels (p < 0.01), as well as increased superoxide dismutase (SOD) activity of CLP rats (p < 0.01). Additionally, TAK-242 treatment improved the condition of CLP rats that had glomerular and tubular injuries and mitochondrial disorders (p < 0.01). Further mechanism research revealed that TAK-242 can inhibit the TLR4/NF-κB signaling pathway activated by CLP (p < 0.01). Above indicators after TAK-242 treatment were close to those of the Sham group. Conclusion TAK-242 can improve oxidative stress, mitochondrial dysfunction, and inflammatory response by inhibiting the activity of TLR4/NF-κB signaling pathway, thereby preventing rats from SA-AKI.

Demystifying Renal Tubular Disorders in children : A simplified approach

Renal tubular disorders essentially include all disorders of the highly specialized channels of the renal tubular system, from the proximal convoluted tubule to the cortical and medullary collecting ducts. This tubular system is responsible for reabsorption of 99% of glomerular ultrafiltrate, which contains a large amount of fluid (approximately 180 L/day) as well as most electrolytes and many metabolites such as glucose (G), amino acids, bicarbonate (HCO3-), phosphate (PO4 3-), and low-molecular-weight proteins and is essential for maintaining fluid, electrolyte, and acid–base balance. In this review, we will briefly discuss when to suspect a renal tubular disorder, a simplified algorithm for evaluation, and specific mutations of a few common disorders.

Research progress on the pharmacological activity and mechanism of chlorogenic acid in alleviating acute kidney injury in sepsis patients

Sepsis-induced acute kidney injury (SAKI) is a serious perioperative complication and a common clinical syndrome characterized by a rapid deterioration in renal function with a high incidence of 70%. The causes of SAKI include impaired mitochondrial function of renal tubular epithelial cells, oxidative stress, inflammatory reaction and renal microcirculation disorder. Chlorogenic acid, as a natural product of plant origin, has various biological activities, such as antibacterial, antiviral, and anti-tumor, and plays a significant role in the treatment of SAKI. This article reviews the pharmacological activities of chlorogenic acid and the signaling pathways involved in relieving SAKI, in order to provide a theoretical basis for in-depth study of the mechanisms underlying the alleviation of SAKI and the confirmation of potential therapeutic targets.

A case of Gitelman syndrome with homozygous SLC12A3 deletion presenting with epilepsy

BackgroundGitelman syndrome (GS) is a rare autosomal recessive hereditary renal tubular disorder characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria.Case presentationWe report a rare case of GS with homozygous loss of SLC12A3 presenting with epilepsy. The patient was a 21-year-old female who sought medical attention for seizures. Her condition primarily manifested as epilepsy, diarrhea, and weakness of limbs. Through genetic analysis, we confirmed the diagnosis of this case and formulated a comprehensive approach for its management.ConclusionsThis case report extends the clinical symptoms of GS and provides a complete family of GS as a reference for subsequent studies.

Coexistence of Neonatal Bartter Syndrome and Congenital Cutis Laxa, in which a new mutation in SLC12A1 was identified

Introduction: Neonatal Bartter Syndrome (NBS) is an extremely rare congenital chronic renal tubular transport disorder characterized by preterm birth, polyhydramnios, polyuria, salt wasting, and severe dehydration. Congenital Cutis Laxa (CCL) is a rare disease characterized by loss of skin flexibility and laxity, and atypical facial appearance.&#x0D; Case Presentation: A 1290-gram female baby at 30+6 weeks of gestation was hospitalized due to premature birth and respiratory distress. During physical examination, an atypical facial appearance, wrinkles on the forehead, skin laxity, and philtrum were visible as well as a small chin and arachnodactyly in the fingers and toes. The patient displayed metabolic alkalosis in her blood gases. The patient, with an atypical face and current findings submitted her exome for genetic diagnosis. Genetic analysis revealed the presence of homozygous NM_001184832.2:c.2485+5G&gt;A (rs749269268) in SLC12A1, and NBS Type 1 was diagnosed. A novel heterozygous NM_000501.4:c.352G&gt;T, p.Val118Phe (rs781922544) variant was detected in ELN, and CCL syndrome with autosomal dominant inheritance was diagnosed.&#x0D; Conclusions: The rare co-occurrence of NBS and CCL syndrome in our patient was seen as a mere coincidence. Since this is the first reported case in the literature, it was deemed appropriate to present this case.

Clinical outcomes of nephrocalcinosis in preschool-age children: association between nephrocalcinosis improvement and long-term kidney function.

We evaluated the long-term clinical outcomes of nephrocalcinosis (NC) according to etiology and grade in preschool-age children with NC. We retrospectively analyzed the clinical outcomes and disease grade of children with NC classified into three groups according to etiology: prematurity, tubular disorders, and others. Overall, 67 children were diagnosed with NC [median age, 0.76 years; interquartile range (IQR) 0.46-2.14 years]. The etiologies of NC included prematurity (28.4%), tubular disorders (25.4%), and others (46.3%). Moreover, 56 (83.6%) children were asymptomatic and diagnosed accidentally through kidney ultrasonography. Newly diagnosed underlying diseases were greater in the tubular disorders group than in the other two groups (P = 0.001). Significantly more newly diagnosed NCs were grade 3 than grade 1 (P = 0.003). The median estimated glomerular filtration rate (eGFR) changed from 96.1 (IQR 68.8-119.2) ml/min/1.72 m2 at diagnosis to 90.9 (IQR 76.4-106.4) ml/min/1.72 m2 at the last follow-up, without a significant difference (P = 0.096). Changes in the kidney function did not differ according to etiology. However, patients without improvement in NC grade showed a decrease in eGFR from 98.1 (IQR 71.1-132.9) to 87.4 (IQR 74.0-104.1) ml/min/1.73 m2 (P = 0.023), while patients with improved NC grade did not show any change in the kidney function. Early recognition, especially in NC grade 3, can help uncover further diagnoses, such as tubular disorders. Long-term kidney function depends on whether the NC grade improves.

Multidisciplinary and multidimensional approaches to transplantation in children with rare genetic kidney diseases.

In this review, we describe the multidisciplinary, multidimensional care required to optimize outcomes for pediatric transplant recipients with rare genetic kidney diseases. Transplant success, recipient survival, and improvement in quality of life depend on collaboration between patients, families, and a team of specialists with medical, as well as nonmedical expertise. A multidisciplinary transplant team composed of experts from medicine, surgery, nursing, nutrition, social services, transplant coordination, psychology, and pharmacology, is now standard in most transplant centers and is critical to the success of a transplant. In addition to these professionals, other specialists, such as cardiologists, urologists, geneticists, metabolic disease specialists, occupational therapists, case management, child life, chaplain, and palliative care services, have a crucial role to play in the preparation, surgery, and follow-up care, especially when a pediatric patient has a rare genetic disorder leading to renal involvement, and the need for transplantation. In order to describe this multidisciplinary care, we divide the genetic renal diseases into five subgroups-metabolic and tubular disorders, glomerular diseases, congenital anomalies of the kidney and urinary tract, ciliopathies including cystic diseases, and miscellaneous renal conditions; and describe for each, the need for care beyond that provided by the standard transplant team members.

BARTTER SYNDROME TYPE I. CLINICAL CASE OF A PREGNANT WOMAN WITH POLYHYDRAMNIOS

Bartter syndrome is an inherited renal tubular disorder characterized by salt wasting, hypokalemia and metabolic acidosis due to impaired salt reabsorption in the ascending limb of the loop of Henle in the renal nephrons. Currently, five types of the disease are known. While the clinical signs of type 3 (classical type) appear in childhood and later ages, types 1, 2, 4, 5 (antenatal type) are characterized by severe polyhydramnios in the antenatal period and antenatal fetal death. This article is about a pregnant woman carrying a fetus with antenatal Bartter syndrome type I.

Clinical utility of genetic testing in Indian children with kidney diseases

BackgroundKidney diseases with genetic etiology in children present with an overlapping spectrum of manifestations. We aimed to analyze the clinical utility of genetic testing in the diagnosis and management of suspected genetic kidney diseases in children.MethodsIn this retrospective study, children ≤ 18 years in whom a genetic test was ordered were included. Clinical indications for genetic testing were categorized as Glomerular diseases, nephrolithiasis and/or nephrocalcinoses, tubulopathies, cystic kidney diseases, congenital abnormality of kidney and urinary tract, chronic kidney disease of unknown aetiology and others. Clinical exome sequencing was the test of choice. Other genetic tests ordered were sanger sequencing, gene panel, multiplex ligation-dependent probe amplification and karyotyping. The pathogenicity of the genetic variant was interpreted as per the American College of Medical Genetics classification.ResultsA total of 86 samples were sent for genetic testing from 76 index children, 8 parents and 2 fetuses. A total of 74 variants were reported in 47 genes. Out of 74 variants, 42 were missense, 9 nonsense, 12 frameshifts, 1 indel, 5 affected the splicing regions and 5 were copy number variants. Thirty-two were homozygous, 36 heterozygous and 6 were hemizygous variants. Twenty-four children (31.6%) had pathogenic and 11 (14.5%) had likely pathogenic variants. Twenty-four children (31.6%) had variants of uncertain significance. No variants were reported in 17 children (22.3%). A genetic diagnosis was made in 35 children with an overall yield of 46%. The diagnostic yield was 29.4% for glomerular diseases, 53.8% for tubular disorders, 81% for nephrolithiasis and/or nephrocalcinoses, 60% for cystic kidney diseases and 50% for chronic kidney disease of unknown etiology. Genetic testing made a new diagnosis or changed the diagnosis in 15 children (19.7%).ConclusionNearly half (46%) of the children tested for a genetic disease had a genetic diagnosis. Genetic testing confirmed the clinical diagnoses, changed the clinical diagnoses or made a new diagnosis which helped in personalized management.

#4875 MANAGEMENT OF TUBULOINTERSTITIAL DISEASE IN PREGNANCY: TEN-YEARS EXPERIENCE OF A NEPHRO-OBSTETRIC CLINIC

Abstract Background and Aims Tubular renal acidosis and salt losing nephropathies are rare conditions but their management during pregnancy that can be challenging due to the physiological adaptation of kidney function. Herein, the authors report the management and outcomes of 7 gestations in patients with Gitelman disease (GS) and renal tubular acidosis (RTA). Method Retrospective analysis of maternal, obstetric and perinatal outcomes of pregnant women with tubulointerstitial diseases surveilled at our Nephro-Obstetric clinic from 2011 to 2021. Results We evaluated 7 pregnancies in 5 women. Mean age was 29 years [21-36]. They were all caucasian. Genetic diagnosis was performed during pregnancy in only one patient. Tubular disorder was caused by Gitelman disease in 3 patients and by renal tubular acidosis in 2 patients (ATP6VA4 and REN genes mutations). There were 4/1 patients in CKD G1/G3a, respectively, and none developed renal function deterioration. Only one patient developed transient proteinuria during both gestations and all patients had a low blood pressure profile. Management during the first trimester was especially challenging in GS patients, due to nausea, vomiting and hyperemesis gravidarum, which required hospital admission for intravenous potassium chloride therapy in all GS patients during the first trimester. Potassium levels in GS patients were generally below normal levels throughout pregnancy (mean 3 meq/L; 2,2-3,4 meq/L), even with progressive increase in therapy. Pre-pregnancy potassium chloride replacement increased from 4–10 tablets of 600 mg/day to a maximum of 9–21 tablets/day. One patient was also treated with spironolactone. The need for oral magnesium slightly increased from 2–3 ampoules of 1500mg/day to 2–4 ampoules/day. GS patients frequently complained of astenia and cramps. Regarding RTA patients, there was also a need to increase sodium bicarbonate dosage from 3–4.5g/day to a maximum of 2–8g /day. Regarding obstetric and perinatal outcomes, none of the patients developed preclampsia, mean gestational age at delivery was 40 weeks (38-41), mean birth weight was 3233g (2775-3825) and mean Apgar score was 10/10/10 at 1st, 5th and 10th minutes respectively. Conclusion In GS patients, management in the first trimester of pregnancy can be challenging due to nausea and vomiting, generally requiring admission for therapy with iv potassium. In spite of increasing doses in oral supplementation, ionic and acid base homeostasis during pregnancy is difficult to achieve. In our small series, maternal, obstetric and perinatal outcomes do not seem to be affected by this unbalance.

#3572 CLINICAL AND GENETIC CHARACTERISTICS OF CHILDREN WITH BARTTER SYNDROME: A SINGLE CENTER LONG-TERM EXPERIENCE

Abstract Background and Aims Bartter syndrome is an autosomal recessive renal tubular disorder. Clinical diagnosis can be challenging due to rarity and phenotypic overlap. Little information is available on a long term follow-up in Bartter syndrome. Our aim was to describe clinical -genetic correlations as well as our experience from the long term follow up of these patients. Method Clinical and genetic characteristics of patients with Bartter syndrome at diagnosis and long term follow up are reported in 19 children. Genetic testing (whole exome sequencing, WES) was done in 14/19 patients. The study period was 17 years (January 1, 2006 to December 31, 2022). Results 16 Caucasian and 3 of gipsy origin (13 boys, 68%) were included. The median age at diagnosis was 0,52 yrs. Median follow up time was 9.8yrs (IQR 6.86-13.8). WES revealed 6 mutations in KCNJ1 genes, 5 in SLC12A1 and 3 in CLCNKB genes. 4 new mutations were identified (3 in KCNJ1 genes and 1 in SLC12A1. 18/19 children were born pre-term (including 2/3 patients with CLCNKB). Nephrocalcinosis was present in 18/19 patients (included the 3 patients with CLCKNB mutations). 4/6 patients with KCNJ1 mutations presented initially with hyperkalemia. Medical treatment in the last follow up included supplementation with potassium in 18, non -steroidal anti-inflammatory agents in 15 and gastroprotective drugs in 13, ramipril in 2. 2/19 received recombinant growth hormone. At last follow up body weight and height were within normal ranges in 16/19 (84%) patients. Hyperparathyroidism (median time of PTH 151.5 pg/ml) have 6/11 (56%) of patients with Bartter I (ΚCNJ1mutation) and Bartter II (SLC12A1 mutation) and only 1/3 with Bartter III (CLCNKB mutation). 2/19 patients have proteinuria. Chronic kidney disease (CKD) occurred in 7/19 (37%) suggesting that the long term prognosis can be unfavorable (4 CKD stage II, 3 CKD stage III). Of note 2 patients with CKD had impaired renal function since diagnosis while the remaining 5 progressed gradually during followup. Conclusion WES is useful in dealing with the phenotypic heterogeneity of Bartter syndrome. Our results emphasize the need for early diagnosis, regular followup and appropriate treatment in order to maintain normal renal function and achieve normal final height and weight.

Generation of a human induced pluripotent stem cell line from a patient with dent disease

Dent disease, an X-linked tubular disorder, is a rare condition that leads to low-molecular-weight proteinuria, hypercalciuria, kidney stones, and chronic kidney disease. Here, we successfully established a human induced pluripotent stem cells (hiPSC) line from peripheral blood mononuclear cells of 10-year-old male with Dent disease 1 caused by the mutation of Chloride Voltage-Gated Channel 5 gene. This hiPSCs displayed features similar to human embryonic stem cells, including pluripotency-associated markers expression, normal karyotype, and the ability to differentiate into cells representing all three germ layers. The implications of this research extend to the potential development of novel treatments for Dent disease.

Gitelman Syndrome – A Case Report

Hypokalaemia is an electrolyte disorder, commonly encountered in clinical practice. Sometimes, it may present with severe life-threatening complications. We present here a case of 22-year-old female, who was admitted to intensive care unit, for severe hypokalaemia associated with cardiac and neurological complications. She had recurrence of such episodes. On detailed clinical and biochemical evaluation, she was diagnosed to have Gitelman syndrome (GS). She was treated with intravenous potassium and magnesium supplementation under cardiac monitoring and other supportive management. She was discharged in stable condition, on oral supplements, and remained stable on follow-up visits. GS is an autosomal recessive and renal tubular disorder characterised by hypokalaemic metabolic alkalosis with hypomagnesaemia, hypocalciuria, secondary hyperreninemic aldosteronism and hypotension. The disease is caused by biallelic inactivating mutations within the SLC12A3 gene encoding the thiazide-sensitive sodium chloride cotransporter expressed within the apical membrane of cells, lining the distal convoluted tubule. Since GS is an autosomal recessive trait, the recurrence risk for people with an affected child is 25%. It is very important to completely evaluate a patient with hypokalaemia to find the underlying cause. There can be various etiological factors for hypokalaemia ranging from common to rare disorders. If underlying aetiology remains undiagnosed, there may be recurrence as well as increased morbidity and mortality. GS is one such disorder, which needs prompt diagnostic evaluation and treatment.

Dent disease manifesting as nephrotic syndrome.

Dent disease is an X-linked recessive renal tubular disorder, which is mainly caused by mutations of the CLCN5 gene and OCRL gene. It is characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis or nephrolithiasis, and progressive renal failure. Nephrotic syndrome is a glomerular disorder characterized by massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia. In this study, we report two cases of Dent disease manifesting as nephrotic syndrome. Two patients were initially diagnosed with nephrotic syndrome due to edema, nephrotic range proteinuria, hypoalbuminemia, and hyperlipidemia, and responded to prednisone and tacrolimus therapy. Genetic testing revealed mutations in the OCRL and CLCN5 genes. They were eventually diagnosed with Dent disease. Nephrotic syndrome is a rare and insidious phenotype of Dent disease, and its pathogenesis is not fully understood. Patients with nephrotic syndrome are recommended to routinely undergo urinary protein classification and urinary calcium testing, especially those with frequently recurrent nephrotic syndrome and poor response to steroid and immunosuppressive therapy. To date, there is no effective drug treatment for Dent disease. About 30% to 80% of patients progress to end-stage renal disease at the age of 30-50.

Clinicopathological Features of Gitelman Syndrome with Proteinuria and Renal Dysfunction

Introduction: Gitelman syndrome (GS) is a rare renal tubular salt-wasting disorder. Besides kidney electrolyte loss, proteinuria and renal dysfunction were also observed. However, their incidence, risk factors, pathological features, and prognosis were unclear. Methods: We retrospectively reviewed 116 GS patients and analyzed their clinical, genetic, and pathological characteristics. We also systematically reviewed articles on GS with proteinuria and renal dysfunction. Results: Twenty-three GS patients had proteinuria (69.6%) and renal dysfunction (43.5%) with a mean age of 35.3 ± 13.2 years, and 65.2% were male. Compared to patients without proteinuria or renal dysfunction, these patients had elevated plasma angiotensin II level (440.2 ± 351.7 vs. 253.2 ± 187.4 pg/mL, p = 0.031) and three times higher incidence of diabetes. The renal pathology of nine biopsied patients indicated hypertrophy of the juxtaglomerular apparatus (100%), chronic tubulointerstitial changes (66.7%), intrarenal vascular changes (66.7%), and glomerulopathy (55.6%). More extensive renin staining was observed in patients with GS than in the control group with glomerular minor lesion (p < 0.001). During a median of 85 months (range, 11–205 months) of follow-up for 19 out of the 23 GS-renal patients, the renal function was generally stable, except one died of cancer and one developed end-stage renal disease because of concomitant membranous nephropathy and IgA nephropathy. Conclusion: Proteinuria and renal dysfunction were more common than expected and might indicate glomerulopathy and vascular lesions besides a tubulointerstitial injury in GS. Renal function may maintain stable with effective therapy in most cases.