Bartter syndrome-like phenotype in a patient with type 2 diabetes mellitus.

Bartter syndrome (BS) is a rare genetic tubulopathy affecting the loop of Henle leading to salt wasting. It is commonly seen in utero or in the early neonatal period. Rare cases of acquired BS are reported in association with infections like tuberculosis, granulomatous conditions like sarcoidosis, autoimmune diseases and drugs. The mainstay of management includes potassium, calcium and magnesium supplementation. We report the case of a woman in her 50s with a history of type 2 diabetes mellitus for the last 10 years, who presented with diabetic foot ulcers and generalised weakness with ECG changes suggestive of hypokalaemia. She had severe hypokalaemia with high urine potassium excretion and hypochloraemic metabolic alkalosis. She poorly responded to intravenously administered potassium supplements and had persistent hypokalaemia. On further evaluation of the persistent hypokalaemia, a diagnosis of idiopathic Bartter-like phenotype was made. She responded well to tablet indomethacin and is presently asymptomatic and is being maintained on tablet indomethacin after 6 months of follow-up.

Pseudo-Bartter syndrome as the initial presentation of cystic fibrosis in children: an important diagnosis not to be missed.

Pseudo-Bartter syndrome (PBS) is characterised by hyponatraemic, hypochloraemic metabolic alkalosis that mimics Bartter syndrome, without renal tubular disease. We present a case of an infant with a positive cystic fibrosis (CF) newborn screening, hospitalised during the summer with dehydration, oliguria and apathy. Blood analysis revealed hypochloraemic metabolic alkalosis, hypokalaemia and hyponatraemia. Urine analysis showed leucocyturia with reduced sodium and chloride excretion fraction, and urinary culture was positive for Citrobacter koseri After antibiotherapy and intravenous rehydration with additional supplementation of sodium and chloride, the patient recovered completely. PBS is one of CF complications that is especially prevalent in infants and young children with increased sweating and/or other causes of additional loss of sodium and chloride. Clinical awareness of this syndrome and its strong clinical suspicion are extremely important for an early diagnosis and treatment of CF, particularly in countries where the universal screening of CF is not routinely performed.

Recurrent transient severe hypocalcaemia in two siblings with type 1 Bartter syndrome.

Type 1 Bartter syndrome causes hypokalaemia and metabolic alkalosis owing to mutation in the SLC12A1 gene. Meanwhile, hypocalcaemia is rare in Bartter syndrome, except in type 5 Bartter syndrome. Herein, we describe two siblings with type 1 Bartter syndrome with recurrent transient severe hypocalcaemia. They each visited our hospital several times with chief complaints of numbness in the limbs, shortness of breath and tetany after stresses such as exercise or fever. Severe hypocalcaemia was also observed with a serum calcium level of approximately 6.0 mg/dL at each visit. The clinical symptoms and abnormalities in laboratory findings quickly improved with rest and intravenous treatment. In a steady state, no severe hypocalcaemia was evident, but serum intact parathyroid hormone (PTH) levels were high. In recent years, a large-scale study has revealed that type 1 and type 2 Bartter syndrome have high PTH values. In addition, there are reports that these patients develop hypocalcaemia due to PTH resistance. Therefore, our patient was also in a PTH-resistant state, and hypocalcaemia was thought to be exacerbated by physical stress. It is not well known that Bartter syndrome patients other than those with type 5 suffer from hypocalcaemia. And hypocalcaemia was not detected in normal examinations under steady-state conditions. Therefore, in patients with type 1 and type 2 Bartter syndrome, severe hypocalcaemia may occur, but may go unnoticed. When following up these patients, the attending physician must keep in mind that such patients are in a PTH-resistant state and that physical stress can cause severe hypocalcaemia.

Bartter Syndrome: A Systematic Review of Case Reports and Case Series.

Background and Objectives: Bartter syndrome (BS) is a rare group of autosomal-recessive disorders that usually presents with hypokalemic metabolic alkalosis, occasionally with hyponatremia and hypochloremia. The clinical presentation of BS is heterogeneous, with a wide variety of genetic variants. The aim of this systematic review was to examine the available literature and provide an overview of the case reports and case series on BS. Materials and Methods: Case reports/series published from April 2012 to April 2022 were searched through Pubmed, JSTOR, Cochrane, ScienceDirect, and DOAJ. Subsequently, the information was extracted in order to characterize the clinical presentation, laboratory results, treatment options, and follow-up of the patients with BS. Results: Overall, 118 patients, 48 case reports, and 9 case series (n = 70) were identified. Out of these, the majority of patients were male (n = 68). A total of 21 patients were born from consanguineous marriages. Most cases were reported from Asia (73.72%) and Europe (15.25%). In total, 100 BS patients displayed the genetic variants, with most of these being reported as Type III (n = 59), followed by Type II (n = 19), Type I (n = 14), Type IV (n = 7), and only 1 as Type V. The most common symptoms included polyuria, polydipsia, vomiting, and dehydration. Some of the commonly used treatments were indomethacin, potassium chloride supplements, and spironolactone. The length of the follow-up time varied from 1 month to 14 years. Conclusions: Our systematic review was able to summarize the clinical characteristics, presentation, and treatment plans of BS patients. The findings from this review can be effectively applied in the diagnosis and patient management of individuals with BS, rendering it a valuable resource for nephrologists in their routine clinical practice.

Pathophysiologic approach in genetic hypokalemia: An update.

The pathophysiology of genetic hypokalemia is close to that of non-genetic hypokalemia. New molecular pathways physiologically involved in renal and extrarenal potassium homeostasis have been highlighted. A physiological approach to diagnosis is illustrated here, with 6 cases. Mechanisms generating and sustaining of hypokalemia are discussed. After excluding acute shift of extracellular potassium to the intracellular compartment, related to hypokalemic periodic paralysis, inappropriate kaliuresis (>40mmol/24h) concomitant to hypokalemia indicates renal potassium wasting. Clinical analysis distinguishes hypertension-associated hypokalemia, due to hypermineralocorticism or related disorders. Genetic hypertensive hypokalemia is rare. It includes familial hyperaldosteronism, Liddle syndrome, apparent mineralocorticoid excess,11beta hydroxylase deficiency and Geller syndrome. In case of normo- or hypo-tensive hypokalemia, two etiologies are to be considered: chloride depletion or salt-wasting tubulopathy. Diarrhea chlorea is a rare disease responsible for intestinal chloride depletion. Due to the severity of hypokalemic metabolic alkalosis, this disease can be misdiagnosed as pseudo-Bartter syndrome. Gitelman syndrome is the most frequent cause of genetic hypokalemia. It typically associates renal sodium and potassium wasting, hypomagnesemia, conserved chloride excretion (>40mmol/24h), and low-range calcium excretion (urinary Ca/creatinine ratio<0.20mmol/mmol). Systematic analysis of hydroelectrolytic disorder and dynamic hormonal investigation optimizes indications for and orientation of genotyping of hereditary salt-losing tubulopathy.

Acquired autoimmune Bartter syndrome in a patient with primary hypothyroidism.

We describe an unusual clinical presentation of autoimmune Bartter syndrome in a patient with primary hypothyroidism. A 65-year-old female patient was admitted with neuromuscular weakness associated with hypokalemia and metabolic alkalosis. She had a suboptimal response to potassium supplementation and potassium-sparing diuretic resulting in re-hospitalization with the same symptoms. A detailed serum and urinary biochemistry analysis in the absence of other causes of potassium wasting helped diagnose Bartter syndrome, a rare entity in adults. An autoimmune profile showed anti-Scl-70 antibody to be positive, although she did not develop other systemic features of the disease. Our patient responded to a steroid-based regimen potassium supplement, Indomethacin, and aldosterone antagonist with remarkable resolution of symptoms and correction of electrolyte derangement. We reviewed the literature to search for similar cases and included twenty-seven full-length publications on acquired and autoimmune causes of Bartter syndrome. Our case highlights the fact that hypokalemia with metabolic alkalosis in an adult patient should prompt clinicians to evaluate for common and uncommon conditions. While assessing for abnormal conditions, acquired Bartter syndrome should be considered if a patient has an underlying autoimmune, endocrine, or connective tissue disease.

Bartter-like Syndrome Induced By Tacrolimus in a Renal Transplanted Boy: A Case Report.

BACKGROUND: Losing-salt tubulopathies, such as Bartter syndrome, are rare and usually inherited due to mutations of tubular reabsorption channels of the nephrons. Despite its scarcity, some cases of acquired losing-salt tubulopathies have been described. In this case report, we discuss the main aspects of Bartter syndrome and present a rare pediatric case of probable tacrolimusinduced Bartter-like syndrome in a renal transplanted boy. CASE PRESENTATION: A ten-year-old male patient with end-stage renal disease due to endo and extra capillary glomerulonephritis was submitted to renal transplantation from a deceased donor. The post-operatory evolution was satisfactory with normalization of serum creatinine levels, mild hypertension, and the absence of metabolic disorders. The immunosuppression protocol included tacrolimus (0.3 mg/kg/day), mycophenolate (455 mg/m2/day) and prednisone (0.5 mg/kg/day). Two months later, the patient was hospitalized due to vomiting, dehydration, intense hypokalemia (1.3 mEq/L), hyponatremia (125 mEq/L), and hypochloremia (84 mmol/L). During hospitalization, he evolved with polydipsia (3000 mL/day) and polyuria (120-160 mL/m2/h) associated with major elevation of urinary potassium excretion, hypercalciuria, mild metabolic alkalosis, hyperfiltration, and proteinuria. The tacrolimus dose was reduced under the suspicion of tubular dysfunction, leading to a better metabolic profile. However, the patient developed a Banff IIb graft rejection, which required pulse therapy and elevation of tacrolimus and mycophenolate doses. Recovery of renal function parameters occurred, but the metabolic disorders worsened following tacrolimus dose elevation. The patient required chronic potassium, chloride, and sodium replacement. CONCLUSION: After administering immunosuppressive medications, physicians should be aware of the possibility of Bartter-like or other losing-salt tubulopathies syndromes that can affect metabolic homeostasis. The suspicion must always be considered in the case of a transplanted patient who presents dehydration and hydroelectrolytic disorders right after the commencement of nephrotoxic immunosuppressive drugs, including tacrolimus and cyclosporine.

Acute Kidney Injury with Severe Metabolic Alkalosis Caused by Habitual Vomiting in an Alcohol Abuser with Pyloric Stenosis.

A 47-year-old man was complaining of consciousness disorder. He had acute kidney injury, hypokalemia, and severe metabolic alkalosis. Initial treatment using intravenous infusion of 0.9% saline and potassium chloride improved his consciousness. It was clarified that he was a severe alcohol abuser who habitually self-vomited. We diagnosed him with volume depletion and pseudo-Bartter's syndrome due to loss of chloride by habitual vomiting. Gastrointestinal endoscopy demonstrated pyloric stenosis, which was ameliorated by Helicobacter pylori eradication therapy. We should consider volume depletion and pseudo-Bartter's syndrome as differential diagnoses when we encounter patients with acute kidney injury and severe metabolic alkalosis.

Pseudo Bartter Syndrome in anorexia nervosa.

INTRODUCTION: Anorexia nervosa is a psychiatric disorder with various non-psychiatric manifestations that arise from the self-imposed malnourishment and possible purging behaviors. These medical manifestations or complications may mimic non psychiatric disorders and difficult the diagnosis of an eating disorder. CASE REPORT: We report the case of a patient with a binge-eating/purging subtype of anorexia nervosa, whose purges consisted in diuretic abuse. She kept her purges secret and during more than 1 year she was admitted several times in the emergency room for, sometimes life-threatening, hypokalemia. Furthermore, she consulted practitioners from different specialties and was hospitalized in a nephrology service to investigate chronic hypokalemia and other metabolic and hydroelectrolytic disturbances. A Bartter Syndrome was suspected, and she underwent genetic testing. Eventually she started psychiatric follow up and was admitted as an inpatient under the care of a specialized eating disorders unit. CONCLUSION: This patient presented a series of metabolic disturbances secondary to the diuretic abuse, that mimicked the manifestations of hereditary tubulopathies like Bartter Syndrome. Coincidentally it was found that the patient had a mutation in a gene linked to Bartter Syndrome, that wasn't enough to justify this diagnosis. So, a Pseudo Bartter Syndrome secondary to the diuretic abuse was evident. The focus on medical manifestations delayed the recognition of the anorexia nervosa and the associated diuretic abuse as the main cause of the electrolyte and metabolic disturbances. This case emphasizes the importance of being familiarized with the non-psychiatric manifestations of eating disorders, so they may be rapidly recognized and managed. LEVEL OF EVIDENCE: Level V, Case Report.

Severe Bartter syndrome type 1: Prompt postnatal management thanks to antenatal identification of SLC12A1 pathogenic variants.

Bartter syndrome (BS) refers to a group of hereditary kidney disorders. One antenatal form is Bartter syndrome type 1 (BS1), caused by pathogenic variants in the SLC12A1 gene. We report a case of BS1 presenting with severe polyhydramnios. The fetus was found to carry three pathogenic variants of SLC12A1, leading to the antenatal diagnosis of BS1 and its prompt management. At age 18 days, clinical conditions were complicated by the onset of sepsis requiring supportive measures as well as steroid and antibiotic therapy. Any newborn with an antenatal history of polyhydramnios or postnatal polyuria should be suspected of having BS, since delayed diagnosis may lead to rapid renal failure.

Late onset Bartter syndrome: Bartter syndrome type 2 presenting with isolated nephrocalcinosis and high parathyroid hormone levels mimicking primary hyperparathyroidism.

OBJECTIVES: Nephrocalcinosis is associated with conditions that cause hypercalcemia and the increased urinary excretion of calcium, phosphate, and/or oxalate. A monogenic etiology is found in almost 30% of childhood-onset nephrocalcinosis which is also a common manifestation of primary hyperparathyroidism. We discuss a child with nephrocalcinosis and features mimicking primary hyperparathyroidism. CASE PRESENTATION: A 7-year-old girl presented with nephrocalcinosis. Hypercalciuria, hyperphosphaturia, mild hypercalcemia, hypophosphatemia and elevated parathyroid hormone levels along with normal serum creatinine and absence of hypokalemic alkalosis suggested primary hyperparathyroidism. However, she was ultimately diagnosed with Bartter syndrome type 2 based on the presence of homozygous pathogenic variation in KCNJ1gene. CONCLUSIONS: This is the second reported case of late-onset Bartter syndrome type 2 without hypokalemic alkalosis. Patients with Bartter syndrome may present with high parathyroid hormone levels and hypercalcemia in addition to hypercalciuria. Thus, the present case suggests that the KCNJ1 gene should be included in genetic analysis even in older children with isolated nephrocalcinosis.

Diagnostic Challenge of Congenital Chloride Diarrhea and Ulcerative Colitis Overlap in an Adult Misdiagnosed with Bartter Syndrome: Case Report and Literature Review.

BACKGROUND Congenital chloride diarrhea (CCD) is an autosomal recessive disease that is usually diagnosed in early childhood. Mutations in the SLC26A3 gene have been attributed to the primary etiology of disease development. Patients with CCD usually present with electrolyte disturbances, metabolic alkalosis, and chronic diarrhea. Early diagnosis is essential to prevent long-term complications that often require genetic testing. Bartter syndrome is another congenital disorder that has clinical features similar to CCD, which might cause a delay in diagnosis in a few patients. CASE REPORT We describe the case of a 28-year-old man who was misdiagnosed as having Bartter syndrome when he was 5 months old based on the clinical features of hypokalemia, metabolic alkalosis, and a family history of Bartter syndrome. He had multiple admissions with diarrhea and was diagnosed with ulcerative colitis. Unfortunately, the course was complicated by renal failure, and the patient underwent a kidney transplant. Persistent metabolic alkalosis with diarrhea after transplantation was unusual in Bartter syndrome. Therefore, his primary diagnosis was challenged and suspicion of CCD was raised, which was confirmed by genetic testing. CONCLUSIONS CCD is a rare congenital disorder that requires high clinical suspicion and often a genetic test to confirm diagnosis. Here, we report a patient who was misdiagnosed as having Bartter syndrome until early adulthood owing to several misleading factors. We hope by reporting this case it will raise awareness about CCD in high-prevalence areas and the importance of early diagnosis to prevent serious complications.

Clinical Course of Patients with Bartter Syndrome.

INTRODUCTION: Bartter syndrome (BS) is a salt losing tubulopathy due to impairment of the transport mechanisms at the thick ascending limb of the Henle's loop. The aim of this study was to report the clinical course of patients with BS. METHODS: Patients with BS were followed from 1996 to 2020 and enrolled to a systematic protocol to confirm primary BS by evaluating the metabolic derangements, nephrolithiasis and nephrocalcinosis. Treatment was based on standard guidelines. Comparisons were made between data at baseline and at the last visit. RESULTS: A total of 13 patients (7 males) with primary BS were analyzed. Two patients had a mutation of the KCNJ1 gene. Age at diagnosis was 3 ± 4.5 years and the follow-up period was 11.19 ± 6.76 years. Metabolic alkalosis was initially detected in 76.92% and remained stable at the last visit (P > .05). Hypokalemia was present in 61.5% of patients at diagnosis, but sustained in 38.46% at the last visit (P < .05). Urine calcium level was 13.3 ± 9.6 mg/ kg/d at the first visit, and significantly reduced to 3.7 ± 2.0 mg/ kg/d at the last visit (P < .05). Nephrocalcinosis was detected by first kidney ultrasonography in 53.8% of patients. Kidney function was preserved, with a glomerular filtration rate of 120.1 ± 28.7 mL/min/ 1.73m2 at last visit. Growth was completely recovered in 71.42% and partially improved in 14.28% of patients after treatment, respectively. All patients received indomethacin and potassium chloride salts. CONCLUSIONS: Long-term follow-up of this cohort of BS showed favorable outcomes after treatment resulting in metabolic normalization and growth catch-up in most patients.  DOI: 10.52547/ijkd.6657.

Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study.

BACKGROUND: Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies. METHODS: Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN). RESULTS: A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs -0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate-standard deviation score < -2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P < .001), suggesting renal phosphate wasting. CONCLUSIONS: Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.

The success of the Cystic Fibrosis Registry of Turkey for improvement of patient care.

BACKGROUND: Cystic fibrosis (CF) registries play an essential role in improving disease outcomes of people with CF. This study aimed to evaluate the association of newly established CF registry system in Turkey on follow-up, clinical, growth, treatment, and complications of people with this disease. METHODS: Age at diagnosis, current age, sex, z-scores of weight, height and body mass index (BMI), neonatal screening results, pulmonary function tests, history of meconium ileus, medications, presence of microorganisms, and follow-up were evaluated and compared to data of people with CF represented in both 2017 and 2019 registry data. RESULTS: There were 1170 people with CF in 2017 and 1637 in 2019 CF registry. Eight hundred and fourteen people were registered in both 2017 and 2019 of whom z-scores of heights and BMI were significantly higher in 2019 (p = 0.002, p =0.039, respectively). Inhaled hypertonic saline, bronchodilator, and azithromycin usages were significantly higher in 2019 (p =0.001, p = 0.001, p = 0.003, respectively). The percent predicted of forced expiratory volume in 1 sec and forced vital capacity were similar in 2017 and 2019 (88% and 89.5%, p = 0.248 and 84.5% and 87%, p =0.332, respectively). Liver diseases and osteoporosis were significantly higher, and pseudo-Bartter syndrome (PBS) was significantly lower in 2019 (p = 0.011, p = 0.001, p = 0.001, respectively). CONCLUSIONS: The z-scores of height and BMI were higher, the use of medications that protect and improve lung functions was higher and incidence of PBS was lower in 2019. It was predicted that registry system increased the care of people with CF regarding their follow-up. The widespread use of national CF registry system across the country may be beneficial for the follow-up of people with CF.