Renal upregulation of NCC counteracts empagliflozin-mediated NHE3 inhibition in normotensive but not in hypertensive male rat.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce blood pressure (BP) in patients with hypertension, yet the precise molecular mechanisms remain elusive. SGLT2i inhibits proximal tubule (PT) NHE3-mediated sodium reabsorption in normotensive rodents, yet no hypotensive effect is observed under this scenario. This study examined the effect of empagliflozin (EMPA) on renal tubular sodium transport in normotensive and spontaneously hypertensive rats (SHRs). It also tested the hypothesis that EMPA-mediated PT NHE3 inhibition in normotensive rats is associated with upregulation of distal nephron apical sodium transporters. EMPA administration for 14 days reduced BP in 12-wk-old SHRs but not in age-matched Wistar rats. PT NHE3 activity was inhibited by EMPA treatment in both Wistar and SHRs. In Wistar rats, EMPA increased NCC activity, mRNA expression, protein abundance, and phosphorylation levels, but not in SHRs. SHRs showed higher NKCC2 activity and an abundance of cleaved ENaC α and γ subunits compared with Wistar rats, none of which were affected by EMPA. Another set of male Wistar rats was treated with EMPA, the NCC inhibitor hydrochlorothiazide (HCTZ), and EMPA combined with HCTZ or vehicle for 14 days. In these rats, BP reduction was observed only with combined EMPA and HCTZ treatment, not with either drug alone. These findings suggest that NCC upregulation counteracts EMPA-mediated inhibition of PT NHE3 in male normotensive rats, maintaining their baseline BP. Moreover, the reduction of NHE3 activity without further upregulation of major apical sodium transporters beyond the PT may contribute to the BP-lowering effect of SGLT2i in experimental models and patients with hypertension.NEW & NOTEWORTHY This study suggests that reduced NHE3-mediated sodium reabsorption in the renal proximal tubule may account, at least in part, for the BP-lowering effect of SGLT2 inhibitors in the setting of hypertension. It also demonstrates that chronic treatment with SGLT2 inhibitors upregulates NCC activity, phosphorylation, and expression in the distal tubule of normotensive but not hypertensive rats. SGLT2 inhibitor-mediated upregulation of NCC seems crucial to counteract proximal tubule natriuresis in subjects with normal BP.

Multiple electrolyte disorders triggered by proton pump inhibitor-induced hypomagnesemia: Case reports with a mini-review of the literature.

Drug-induced hypomagnesemia is an adverse effect with the potential for serious and fatal outcomes. Although rare, chronic use of proton pump inhibitors (PPIs) can cause hypomagnesemia due to impaired intestinal absorption, mainly attributed to reduced transcellular transport of magnesium via transient receptor potential melastatin 6 (TRPM6) and 7 (TRPM7) channels. However, a reduction of magnesium paracellular absorption due to the downregulation of intestinal claudins has also been reported. PPI-induced hypomagnesemia can trigger other concomitant electrolyte derangements, including hypokalemia, hypocalcemia, hypophosphatemia, and hyponatremia. Here we report two cases of multiple electrolyte disorders associated with PPI-induced hypomagnesemia, the clinical manifestations of which were cardiac arrhythmia, cognitive changes, and seizure crisis. These cases illustrate the need to monitor serum magnesium levels in patients on long-term PPI use, especially in the elderly and those with malabsorptive bowel syndromes or taking loop diuretics and thiazides.

Chikungunya virus as a trigger for different renal disorders: an exploratory study.

INTRODUCTION: Chikungunya virus was detected in cases of acute chikungunya fever in renal tissue. However, chikungunya virus-related kidney injury still lacks characterization, and it is unknown whether the kidneys are reservoirs for the virus. We sought to detect histopathological changes and viral antigens in renal tissue, and to evaluate kidney injury markers in different phases of chikungunya fever. METHODS: Two groups were evaluated in this exploratory study: patients with biopsy-proven kidney injury established after chikungunya fever, and patients with post-chikungunya fever chronic joint manifestations without known kidney injury, in whom we actively searched for kidney injury markers. RESULTS: In the first group, 15 patients had kidney injury 0.5-24 months after chikungunya fever. The most frequent histopathological diagnoses were glomerular lesions. No viral antigens were detected in renal tissue. High-risk genotypes were detected in patients with atypical hemolytic uremic syndrome and focal and segmental glomerulosclerosis. In the second group, 114 patients had post-chikungunya fever joint manifestations on average for 35.6 months. Mean creatinine and proteinuria were 0.9 mg/dl and 71.5 mg/day, respectively. One patient had isolated hematuria. There was no indication for renal biopsy in this group. CONCLUSIONS: Several histopathological features were found after chikungunya fever, without virus detection in renal tissue. These findings suggest that chikungunya virus may trigger kidney lesions with varying degrees of severity at different stages of infection. However, the probability that this virus replicates in the renal tissue seems unlikely.

Tenofovir-induced renal and bone toxicity: report of two cases and literature review.

Tenofovir Disoproxil Fumarate (TDF) is one of the drugs in the initial first-line antiretroviral regimen for the treatment of hepatitis B and HIV infections. Despite its effectiveness and few adverse effects, it is related to renal and bone toxicity. We described two cases of HIV-positive middle-aged women who had been using TDF for two and four years (cases 1 and 2, respectively) and were admitted to the emergency room. Case 1 presented with metabolic ileum and diffuse bone pain while case 2 presented with bilateral coxo-femoral pain after a fall from standing height. Both cases had similar laboratory tests: hyperchloremic metabolic acidosis, hypophosphatemia, hypokalemia, hypouricemia and elevated plasma creatinine. In urinary exams, there was evidence of renal loss of electrolytes, justifying the serum alterations, in addition to glucosuria and proteinuria. The bone pain investigation identified bone fractures and reduced bone mineral density, together with increased levels of parathyroid hormone, alkaline phosphatase and vitamin D deficiency. These two cases illustrate the spectrum of adverse renal and bone effects associated with TDF use. TDF was discontinued and treatment was focused on correcting the electrolyte disturbances and acidosis, in addition to controlling the bone disease through vitamin D and calcium supplementation. The renal changes found in both cases characterized the Fanconi's syndrome, and occurred due to TDF toxicity to proximal tubule cells mitochondria. Bone toxicity occurred due to direct interference of TDF in bone homeostasis, in addition to vitamin D deficiency and phosphaturia resulting from tubulopathy. During the follow-up, both cases evolved with chronic kidney disease and in one of them, the Fanconi's syndrome did not revert. We emphasize the need to monitor markers of bone metabolism and glomerular and tubular functions in patients using TDF.

The "new normal" osmotic threshold: Osmostat reset.

Hyponatremia is the most common electrolyte disorder in hospitalized patients. The syndrome of inappropriate antidiuresis (SIAD) is one of the leading causes of hyponatremia. Although not widely known, SIAD has a vast spectrum of etiologies and differential diagnoses and has been classically divided into four types (A, B, C, D). Frequently, when we use the term SIAD in clinical practice, it refers to subtype A, the so-called classic SIAD. The purpose of reporting this case is to make the clinicians aware of a specific subtype of SIAD, type C, an underdiagnosed entity called osmostat reset (OR). Due to similarities, OR often ends up being misinterpreted as classic SIAD. However, the differentiation between these two entities is crucial due to treatment implications. This manuscript highlights the use of an algorithm, based on the fraction of uric acid excretion, as an approach to the differential diagnosis of hyponatremia.

Paracrine and endocrine regulation of renal K+ secretion.

The seminal studies conducted by Giebisch and coworkers in the 1960s paved the way for understanding the renal mechanisms involved in K+ homeostasis. It was demonstrated that differential handling of K+ in the distal segments of the nephron is crucial for proper K+ balance. Although aldosterone had been classically ascribed as the major ion transport regulator in the distal nephron, thereby contributing to K+ homeostasis, it became clear that aldosterone per se could not explain the ability of the kidney to modulate kaliuresis in both acute and chronic settings. The existence of alternative kaliuretic and antikaliuretic mechanisms was suggested by physiological studies in the 1980s but only gained form and shape with the advent of molecular biology. It is now established that the kidneys recruit several endocrine and paracrine mechanisms for adequate kaliuretic response. These mechanisms include the direct effects of peritubular K+, a gut-kidney regulatory axis sensing dietary K+ levels, the kidney secretion of kallikrein during postprandial periods, the upregulation of angiotensin II receptors in the distal nephron during chronic changes in K+ diet, and the local increase of prostaglandins by low-K+ diet. This review discusses recent advances in the understanding of endocrine and paracrine mechanisms underlying the modulation of K+ secretion and how these mechanisms impact kaliuresis and K+ balance. We also highlight important unknowns about the regulation of renal K+ excretion under physiological circumstances.

Tenofovir-induced renal and bone toxicity: report of two cases and literature review

ABSTRACT Tenofovir Disoproxil Fumarate (TDF) is one of the drugs in the initial first-line antiretroviral regimen for the treatment of hepatitis B and HIV infections. Despite its effectiveness and few adverse effects, it is related to renal and bone toxicity. We described two cases of HIV-positive middle-aged women who had been using TDF for two and four years (cases 1 and 2, respectively) and were admitted to the emergency room. Case 1 presented with metabolic ileum and diffuse bone pain while case 2 presented with bilateral coxo-femoral pain after a fall from standing height. Both cases had similar laboratory tests: hyperchloremic metabolic acidosis, hypophosphatemia, hypokalemia, hypouricemia and elevated plasma creatinine. In urinary exams, there was evidence of renal loss of electrolytes, justifying the serum alterations, in addition to glucosuria and proteinuria. The bone pain investigation identified bone fractures and reduced bone mineral density, together with increased levels of parathyroid hormone, alkaline phosphatase and vitamin D deficiency. These two cases illustrate the spectrum of adverse renal and bone effects associated with TDF use. TDF was discontinued and treatment was focused on correcting the electrolyte disturbances and acidosis, in addition to controlling the bone disease through vitamin D and calcium supplementation. The renal changes found in both cases characterized the Fanconi's syndrome, and occurred due to TDF toxicity to proximal tubule cells mitochondria. Bone toxicity occurred due to direct interference of TDF in bone homeostasis, in addition to vitamin D deficiency and phosphaturia resulting from tubulopathy. During the follow-up, both cases evolved with chronic kidney disease and in one of them, the Fanconi's syndrome did not revert. We emphasize the need to monitor markers of bone metabolism and glomerular and tubular functions in patients using TDF.

High blood pressure induced by vitamin D deficiency is associated with renal overexpression and hyperphosphorylation of Na+-K+-2Cl- cotransporter type 2.

OBJECTIVES: Clinical and epidemiological studies have suggested a correlation between vitamin D deficiency (VDD) and high blood pressure (BP). This study aimed to test the hypothesis that high BP induced by VDD is associated with altered expression and covalent modification of apical sodium transporters along the nephron. The contributions of the intrarenal renin-angiotensin system (RAS) and oxidative stress were also investigated. METHODS: Male Wistar rats were fed a vitamin D-free (n = 26) or standard diet (n = 25) for 30 days. BP was recorded using noninvasive and invasive procedures. The expression levels of total and phosphorylated apical sodium transporters in rat renal cortex and medulla were evaluated by immunoblotting. Intrarenal RAS components were assessed by immunoblotting and ELISA. Renal oxidative stress was analyzed by measuring the concentrations of thiobarbituric acid reactive substances and reduced glutathione. RESULTS: Higher BP levels in VDD rats than controls were accompanied by overexpression and hyperphosphorylation of renal cortical and medullary Na+-K+-2Cl- cotransporter type 2, enhanced levels of phosphorylated Na+/H+ exchanger type 3, and reduced expression levels of total and phosphorylated Na+/Cl- cotransporter. Changes in intrarenal RAS induced by VDD vs. controls included the marked elevation of medullary renin expression, higher expression of cortical angiotensinogen, higher urinary angiotensinogen excretion, and higher cortical and medullary angiotensin II content. VDD rats displayed higher thiobarbituric acid reactive substances/glutathione ratios in the renal cortex and medulla than controls. CONCLUSION: These results suggest that the molecular mechanisms underlying the effects of VDD on BP may include the upregulation of Na+-K+-2Cl- cotransporter type 2 and activation of intrarenal RAS and oxidative stress.

Urinary DPP4 correlates with renal dysfunction, and DPP4 inhibition protects against the reduction in megalin and podocin expression in experimental CKD.

This study investigated the molecular mechanisms underlying the antiproteinuric effect of DPP4 inhibition in 5/6 renal ablation rats and tested the hypothesis that the urinary activity of DPP4 correlates with chronic kidney disease (CKD) progression. Experiments were conducted in male Wistar rats who underwent 5/6 nephrectomy (Nx) or sham operation followed by 8 wk of treatment with the DPP4 inhibitor (DPP4i) sitagliptin or vehicle. Proteinuria increased progressively in Nx rats throughout the observation period. This increase was remarkably mitigated by sitagliptin. Higher levels of proteinuria in Nx rats compared to control rats were accompanied by higher urinary excretion of retinol-binding protein 4, a marker of tubular proteinuria, as well as higher urinary levels of podocin, a marker of glomerular proteinuria. Retinol-binding protein 4 and podocin were not detected in the urine of Nx + DPP4i rats. Tubular and glomerular proteinuria was associated with the reduced expression of megalin and podocin in the renal cortex of Nx rats. Sitagliptin treatment partially prevented this decrease. Besides, the angiotensin II renal content was significantly reduced in the Nx rats that received sitagliptin compared to vehicle-treated Nx rats. Interestingly, both urinary DPP4 activity and abundance increased progressively in Nx rats. Additionally, urinary DPP4 activity correlated positively with serum creatinine levels, proteinuria, and blood pressure. Collectively, these results suggest that DPP4 inhibition ameliorated both tubular and glomerular proteinuria and prevented the reduction of megalin and podocin expression in CKD rats. Furthermore, these findings suggest that urinary DPP4 activity may serve as a biomarker of renal disease and progression.

Brazilian Consortium for the Study on Renal Diseases Associated With COVID-19: A Multicentric Effort to Understand SARS-CoV-2-Related Nephropathy.

Kidney involvement appears to be frequent in coronavirus disease 2019 (COVID-19). Despite this, information concerning renal involvement in COVID-19 is still scarce. Several mechanisms appear to be involved in the complex relationship between the virus and the kidney. Also, different morphological patterns have been described in the kidneys of patients with COVID-19. For some authors, however, this association may be just a coincidence. To investigate this issue, we propose assessing renal morphology associated with COVID-19 at the renal pathology reference center of federal university hospitals in Brazil. Data will come from a consortium involving 17 federal university hospitals belonging to Empresa Brasileira de Serviços Hospitalares (EBSERH) network, as well as some state hospitals and an autopsy center. All biopsies will be sent to the referral center for renal pathology of the EBSERH network. The data will include patients who had coronavirus disease, both alive and deceased, with or without pre-existing kidney disease. Kidney biopsies will be analyzed by light, fluorescence, and electron microscopy. Furthermore, immunohistochemical (IHC) staining for various inflammatory cells (i.e., cells expressing CD3, CD20, CD4, CD8, CD138, CD68, and CD57) as well as angiotensin-converting enzyme 2 (ACE2) will be performed on paraffinized tissue sections. In addition to ultrastructural assays, in situ hybridization (ISH), IHC and reverse transcription-polymerase chain reaction (RT-PCR) will be used to detect Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) in renal tissue. For the patients diagnosed with Collapsing Glomerulopathy, peripheral blood will be collected for apolipoprotein L-1 (APOL1) genotyping. For patients with thrombotic microangiopathy, thrombospondin type 1 motif, member 13 (ADAMTS13), antiphospholipid, and complement panel will be performed. The setting of this study is Brazil, which is second behind the United States in highest confirmed cases and deaths. With this complete approach, we hope to help define the spectrum and impact, whether immediate or long-term, of kidney injury caused by SARS-CoV-2.

Takotsubo Cardiomyopathy in an Alzheimer Disease Patient: The Potential Contribution of Antidepressant Agents.

Takotsubo cardiomyopathy (TC) is an acute cardiac dysfunction, clinically similar to myocardial ischemia. The physiopathology of the syndrome seems to be related to excessive sympathetic activity that is triggered by physical or emotional stress factors. We report the case of an 83-year-old woman with advanced Alzheimer disease who had recently used nortriptyline and sertraline and was admitted with chest pain. An electrocardiogram showed ST-elevation, and markers of myocardial necrosis were slightly increased. However, coronariography did not demonstrate stenotic lesions. Transthoracic echocardiography and ventriculography identified decreased ventricular function, apical akinesia, and compensatory hyperkinesia of other segments that were compatible with TC. The patient evolved with cardiogenic shock and died. Alzheimer patients may be more susceptible to develop TC, both because of the disease itself and because of the multiple medications they are exposed to that increase catecholamine levels. In this case, antidepressant drugs were considered to be a potential factor that enhanced the susceptibility.

The role of urea-induced osmotic diuresis and hypernatremia in a critically ill patient: case report and literature review.

Hypernatremia is a common electrolyte problem at the intensive care setting, with a prevalence that can reach up to 25%. It is associated with a longer hospital stay and is an independent risk factor for mortality. We report a case of hypernatremia of multifactorial origin in the intensive care setting, emphasizing the role of osmotic diuresis due to excessive urea generation, an underdiagnosed and a not well-known cause of hypernatremia. This scenario may occur in patients using high doses of corticosteroids, with gastrointestinal bleeding, under diets and hyperprotein supplements, and with hypercatabolism, especially during the recovery phase of renal injury. Through the present teaching case, we discuss a clinical approach to the diagnosis of urea-induced osmotic diuresis and hypernatremia, highlighting the utility of the electrolyte-free water clearance concept in understanding the development of hypernatremia.

Chronic Inflammatory Arthropathy Preceding Acute Systemic Manifestations of Sarcoidosis: A Possible Overlap of Idiopathic Juvenile Arthritis and Sarcoidosis.

Sarcoidosis is a multisystem disease with unknown etiology, marked by T lymphocytes and macrophages agglomeration, which leads to the formation of noncaseating granulomas in the affected tissues. We describe a case of a 40-year-old black patient referred to our service for evaluation of nephrolithiasis and persistent elevation of plasma creatinine. He reported important weight loss, fever episodes, and abdominal and low back intermittent pain in the past 6 months. The investigation revealed elevated serum calcium level, hepatosplenomegaly, retroperitoneal lymphadenopathy, anemia, thrombocytopenia, and nephrolithiasis. The initial diagnostic hypothesis was lymphoproliferative disease, but the laparoscopic propaedeutic showed multiple white lesions on the liver surface, which biopsy identified as noncaseating granulomas with asteroid corpuscles, suggestive of sarcoidosis. He was treated with corticosteroids with significant improvement in symptoms and in calcium and creatinine levels. Besides, the patient presented a long-term large joints arthropathy, especially on the knees (with bilateral prosthesis), wrists, and ankles, of unknown etiology. We discuss the systemic manifestations of sarcoidosis related to the reported case, as well as the possible overlapping of idiopathic juvenile arthritis with sarcoidosis.

Atypical presentation of familial hypomagnesemia with hypercalciuria and nephrocalcinosis in a patient with a new claudin-16 gene mutation.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive tubular disorder caused by mutations in genes that encode renal tight junction proteins claudin-16 or claudin-19, which are responsible for magnesium and calcium paracellular reabsorption in the thick ascending limb of Henle's loop. Progressive renal failure is frequently present, and most of the patients require renal replacement therapy still during adolescence. In this case report, we describe a new homozygous missense mutation on CLDN16 gene (c.592G>C, Gly198Arg) in a 24-year-old male patient diagnosed with FHHNC after clinical investigation due to incidental detection of altered routine laboratorial tests, who was firstly misdiagnosed with primary hyperparathyroidism. In addition, it illustrates an atypical presentation of this disease, with late onset of chronic kidney disease, improving the phenotype-genotype knowledge of patients with FHHNC.

Cardioprotection Conferred by Sitagliptin Is Associated with Reduced Cardiac Angiotensin II/Angiotensin-(1-7) Balance in Experimental Chronic Kidney Disease.

Dipeptidyl peptidase IV (DPPIV) inhibitors are antidiabetic agents that exert renoprotective actions independently of glucose lowering. Cardiac dysfunction is one of the main outcomes of chronic kidney disease (CKD); however, the effects of DPPIV inhibition on cardiac impairment during CKD progression remain elusive. This study investigated whether DPPIV inhibition mitigates cardiac dysfunction and remodeling in rats with a 5/6 renal ablation and evaluated if these effects are associated with changes in the cardiac renin-angiotensin system (RAS). To this end, male Wistar rats underwent a 5/6 nephrectomy (Nx) or sham operation, followed by an 8-week treatment period with the DPPIV inhibitor sitagliptin (IDPPIV) or vehicle. Nx rats had lower glomerular filtration rate, overt albuminuria and higher blood pressure compared to sham rats, whereas CKD progression was attenuated in Nx + IDPPIV rats. Additionally, Nx rats exhibited cardiac hypertrophy and fibrosis, which were associated with higher cardiac DPPIV activity and expression. The sitagliptin treatment prevented cardiac fibrosis and mitigated cardiac hypertrophy. The isovolumic relaxation time (IRVT) was higher in Nx than in sham rats, which was suggestive of CKD-associated-diastolic dysfunction. Sitagliptin significantly attenuated the increase in IRVT. Levels of angiotensin II (Ang II) in the heart tissue from Nx rats were higher while those of angiotensin-(1-7) Ang-(1-7) were lower than that in sham rats. This cardiac hormonal imbalance was completely prevented by sitagliptin. Collectively, these results suggest that DPPIV inhibition may delay the onset of cardiovascular impairment in CKD. Furthermore, these findings strengthen the hypothesis that a crosstalk between DPPIV and the renin-angiotensin system plays a role in the pathophysiology of cardiorenal syndromes.

A physiology-based approach to a patient with hyperkalemic renal tubular acidosis / Abordagem diagnóstica de um paciente com acidose tubular renal hipercalêmica

ABSTRACT Hyperkalemic renal tubular acidosis is a non-anion gap metabolic acidosis that invariably indicates an abnormality in potassium, ammonium, and hydrogen ion secretion. In clinical practice, it is usually attributed to real or apparent hypoaldosteronism caused by diseases or drug toxicity. We describe a 54-year-old liver transplant patient that was admitted with flaccid muscle weakness associated with plasma potassium level of 9.25 mEq/L. Additional investigation revealed type 4 renal tubular acidosis and marked hypomagnesemia with high fractional excretion of magnesium. Relevant past medical history included a recent diagnosis of Paracoccidioidomycosis, a systemic fungal infection that is endemic in some parts of South America, and his outpatient medications contained trimethoprim-sulfamethoxazole, tacrolimus, and propranolol. In the present acid-base and electrolyte case study, we discuss a clinical approach for the diagnosis of hyperkalemic renal tubular acidosis and review the pathophysiology of this disorder.

RESUMO A acidose tubular renal hipercalêmica é uma acidose metabólica de ânion gap normal que invariavelmente indica anormalidade na secreção de íons potássio, amônio e hidrogênio. Na prática clínica, está geralmente atribuída a um estado de hipoaldosteronismo real ou aparente, causado por doenças ou toxicidade por drogas. Descrevemos um paciente de 54 anos, transplantado hepático, que foi admitido com fraqueza muscular associada à hipercalemia, potássio plasmático de 9,25 mEq/L. A investigação adicional revelou acidose tubular renal tipo 4 e importante hipomagnesemia com elevada fração de excreção de magnésio. A história patológica pregressa incluía um diagnóstico recente de Paracoccidioidomicose - uma infecção sistêmica fúngica endêmica que ocorre em algumas partes da América do Sul -, e as medicações de uso habitual continham sulfametoxazol-trimetoprim, tacrolimus e propranolol. No presente relato de caso, discutiremos uma abordagem clínico-laboratorial para o diagnóstico da acidose tubular renal hipercalêmica, assim como da hipomagnesemia, revisando a fisiopatologia desses transtornos.

A physiology-based approach to a patient with hyperkalemic renal tubular acidosis.

Hyperkalemic renal tubular acidosis is a non-anion gap metabolic acidosis that invariably indicates an abnormality in potassium, ammonium, and hydrogen ion secretion. In clinical practice, it is usually attributed to real or apparent hypoaldosteronism caused by diseases or drug toxicity. We describe a 54-year-old liver transplant patient that was admitted with flaccid muscle weakness associated with plasma potassium level of 9.25 mEq/L. Additional investigation revealed type 4 renal tubular acidosis and marked hypomagnesemia with high fractional excretion of magnesium. Relevant past medical history included a recent diagnosis of Paracoccidioidomycosis, a systemic fungal infection that is endemic in some parts of South America, and his outpatient medications contained trimethoprim-sulfamethoxazole, tacrolimus, and propranolol. In the present acid-base and electrolyte case study, we discuss a clinical approach for the diagnosis of hyperkalemic renal tubular acidosis and review the pathophysiology of this disorder.

Distribution of Serum Uric Acid in Black Africans and Its Association With Cardiovascular Risk Factors.

Hyperuricemia is associated with cardiovascular disease and its prevalence is unknown in black Africans. This study reports hyperuricemia distribution and its association with cardiovascular risk factors in a selected Angolan population. A cross-sectional study in 585 black Africans was performed. Hyperuricemia was defined as uric acid >7.0 mg/dL in men or >5.7 mg/dL in women. Overall prevalence was 25%. Hyperuricemia was associated with hypertension (odds ratio [OR], 2.20; confidence interval [CI], 95% 1.41-3.47), high waist circumference (OR, 1.67; CI, 95% 1.05-2.65), and metabolic syndrome (OR, 1.66; CI, 95% 1.07-2.57). Compared to those with uric acid levels in the first quartile, individuals in the fourth quartile showed higher body mass index, waist circumference, systolic blood pressure, and plasma levels of creatinine and triglycerides. Hypertension, high waist circumference, and metabolic syndrome were the major cardiovascular risk factors associated with hyperuricemia.

N-acetylcysteine protects against star fruit-induced acute kidney injury.

BACKGROUND: Star fruit (SF) is a popular fruit, commonly cultivated in many tropical countries, that contains large amount of oxalate. Acute oxalate nephropathy and direct renal tubular damage through release of free radicals are the main mechanisms involved in SF-induced acute kidney injury (AKI). The aim of this study was to evaluate the protective effect of N-acetylcysteine (NAC) on SF-induced nephrotoxicity due to its potent antioxidant effect. MATERIALS AND METHODS: Male Wistar rats received SF juice (4 mL/100 g body weight) by gavage after a 12 h fasting and water deprivation. Fasting and water deprivation continued for 6 h thereafter to warrant juice absorption. Thereafter, animals were allocated to three experimental groups: SF (n = 6): received tap water; SF + NAC (n = 6): received NAC (4.8 g/L) in drinking water for 48 h after gavage; and Sham (n = 6): no interventions. After 48 h, inulin clearance studies were performed to determine glomerular filtration rate. In a second series of experiment, rats were housed in metabolic cages for additional assessments. RESULTS: SF rats showed markedly reduced inulin clearance associated with hyperoxaluria, renal tubular damage, increased oxidative stress and inflammation. NAC treatment ameliorated all these alterations. Under polarized light microscopy, SF rats exhibited intense calcium oxalate birefringence crystals deposition, dilation of renal tubules and tubular epithelial degeneration, which were attenuate by NAC therapy. CONCLUSIONS: Our data show that therapeutic NAC attenuates renal dysfunction in a model of acute oxalate nephropathy following SF ingestion by reducing oxidative stress, oxaluria, and inflammation. This might represent a novel indication of NAC for the treatment of SF-induced AKI.