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The common finding of hypokalemic alkalosis in several unrelated disorders may confound the early diagnosis of salt-losing tubulopathy (SLT). Antenatal Bartter syndrome (BS) must be considered in idiopathic early-onset polyhydramnios. Fetal megabladder in BS may allow its distinction from third-trimester polyhydramnios that occurs in congenital chloride diarrhea (CCD). Fetal megacolon occurs in CCD while fecal chloride >90 mEq/L in infants is diagnostic. Failure-to-thrive, polydipsia and polyuria in early childhood are the hallmarks of classic BS. Unlike BS, there is low urinary chloride in hypokalemic alkalosis of intractable emesis and cystic fibrosis. Rarely, renal salt wasting may result from cystinosis, Dent disease, disorders of paracellular claudin-10b and Kir4.1 potassium-channel deficiency. Acquired BS may result from calcimimetic up-regulation of a calcium-sensing receptor or autoantibody inactivation of sodium chloride co-transporters in Sjögren syndrome. A relatively common event of heterozygous gene mutations for Gitelman syndrome increases the likelihood of its random occurrence in certain diseases of adult onset. Finally, diuretic abuse is the most common differential diagnosis of SLT. Unlike the persistent elevation in BS, urinary chloride concentration losses waxes and wanes on day-to-day assessment in patients with diuretic misuse.Nephrologists are familiar with severe cases of anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV) presenting as rapidly progressive glomerulonephritis. However, less is known about AAV with slowly progressive renal involvement. While its existence is acknowledged in textbooks, much remains unknown regarding its relative frequency versus more aggressive cases as well as about the optimal therapeutic approach and response to therapy. Moreover, this uncommon presentation may be underdiagnosed, given the scarce familiarity of physicians. In this issue of Clinical Kidney Journal, Trivioli et al. report the largest series to date and first systematic assessment of patients with AAV and slowly progressive renal involvement, defined as a reduction in estimated glomerular filtration rate (eGFR) of 25-50% in the 6 months prior to diagnosis after excluding secondary causes. Key findings are that slowly progressive AAV may be less common than previously thought, although it still represents the second most common presentation of renal AAV, it usually has a microscopic polyangiitis, anti-myeloperoxidase, mainly renal phenotype in elderly individuals, diagnosis may be late (over one-third of patients had end-stage kidney disease at diagnosis), clearly identifying an unmet need for physician awareness about this presentation, but those not needing renal replacement therapy at diagnosis still responded to immunosuppression.Tyrosine kinase receptor inhibitors (TKIs) are a relatively new class of targeted anti-cancer agents with vascular endothelial growth factor signalling pathway-inhibiting properties. Hypertension is recognized as one of the most common adverse effects of this anti-angiogenic therapy and is the consequence of reduced production of vasodilatory nitric oxide and reduced prostacyclin production as well as increased production of vasoconstrictive endothelin-1. TKI-induced hypertension is dose dependent and it has been suggested as a marker of treatment effectiveness. In this issue, Saito et al. report the incidence of treatment-related hypertension in patients treated with lenvatinib, a newer TKI, for non-resectable hepatocellular carcinoma. The authors demonstrate that a subset of TKI-treated patients develop fluid retention 3 weeks after treatment initiation as a consequence of lower urinary sodium excretion and thus provides insights into the pathogenesis of blood pressure elevation in the second phase. These findings contribute to a better understanding of TKI-associated hypertension and help in choosing the most appropriate antihypertensive agents in this setting. Active control of hypertension may help more patients benefit from longer TKI therapy, possibly resulting in better cancer outcomes.Atrial fibrillation (AF) is common in patients with chronic kidney disease (CKD), affecting 10-25% of patients requiring dialysis. Compared with the general population, patients requiring dialysis are also at increased risk of stroke, the major thromboembolic complication of AF. The evidence base for management strategies of AF specific to patients with advanced CKD is limited and not informed by randomized controlled trials. These gaps in evidence encompass rate and rhythm control strategies as well as a paucity of data informing which patients should receive anticoagulation. The European Renal Association-European Dialysis and Transplant Association and European Heart Rhythm Association undertook a survey of nephrologists and cardiologists exploring management strategies in patients with AF and CKD. We review the results of this survey, highlighting the differences in clinical approaches from cardiologists and nephrologists to these conditions. Closer collaboration between these specialties should lead to improved outcomes for patients with advanced CKD and AF. Specific issues that will need to be addressed may include healthcare burden to patients, location of clinics compared with dialysis sites and awareness of complications of treatments specific to CKD, such as calciphylaxis associated with vitamin K antagonism.Age-standardized rates of diabetes mellitus (DM)-related complications, such as acute myocardial infarction, stroke or amputations, have decreased in recent years, but this was not associated with a clear reduction of the incidence of advanced chronic kidney disease (CKD) requiring renal replacement therapy. The early detection of diabetic kidney disease (DKD) is a key to reduce complications, morbidity and mortality. Consensus documents and clinical practice guidelines recommend referral of DM patients to nephrology when the estimated glomerular filtration rate falls below 30 mL/min/1.73 m2 or when albuminuria exceeds 300 mg/g urinary creatinine. https://www.selleckchem.com/products/monocrotaline.html Conceptually, it strikes as odd that patients with CKD are referred to the specialist caring for the prevention and treatment of CKD only when >70% of the functioning kidney mass has been lost. The increasing global health burden of CKD, driven in large part by DKD, the suboptimal impact of routine care on DKD outcomes as compared with other DM complications, the realization that successful therapy of CKD requires early diagnosis and intervention, the advances in earlier diagnosis of kidney injury and the recent availability of antidiabetic drugs with a renal mechanism of action and lack of hypoglycaemia risk, which additionally are cardio- and nephroprotective, all point towards a paradigm shift in the care for DM patients in which they should be referred earlier to nephrology as part of a coordinated and integrated care approach.
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