SUMMARY AT A GLANCEN-benzylpiperazine (BZP) is a popular recreational party drug. There is a potential for acute kidney injury, and this needs to be considered when any individual presents with symptoms of recreational drug overdose with 3,4-methylenedioxymethamphetamine (MDMA) and/or BZP components. ABSTRACT:N-benzylpiperazine (BZP) is the active ingredient in recreational 'party' pills with a stimulant, euphoric mechanism of action akin to that of 3,4-methylenedioxymethamphetamine (MDMA or ecstasy). Many people (ab)use BZP-based party pills usually without any significant toxic effects. However, nephrotoxicity secondary to hyperthermia and rhabdomyolysis has been reported. Another serious renal-related side-effect is hyponatraemia with acute cerebral oedema. There is also evidence that these agents may have a specific toxic effect producing acute kidney injury. Thus, acute kidney injury either direct or secondary to the effects of BZP or MDMA need to be considered when any individual presents with symptoms of a recreational party drug overdose.

Syphilis is a sexually transmitted disease caused by spirochaete Treponema pallidum. The incidence of syphilis is rising across the globe. It has been described in the literature as a great imitator due to the vast range of clinical manifestations that can occur in the disease. Renal manifestations are rare but a feature of secondary syphilis. It can cause glomerulopathies, tubular pathology and vasculitic lesions in the kidney. Membranous nephropathy is the most commonly reported glomerular lesion associated with syphilis. With two recent cases of secondary membranous nephropathy due to syphilis, it is timely to review the current state of knowledge, and discuss the different renal manifestation of syphilis, its pathology and treatment options.

IntroductionSympathetic neural activation is markedly increased in end-stage kidney disease (ESKD). Catheter-based renal denervation (RDN) reduces sympathetic overactivity and blood pressure in resistant hypertension. We investigated the effect of RDN on sympathetic neural activation and left ventricular mass in patients with ESKD.MethodsNine ESKD (6 hemodialysis and 3 peritoneal dialysis) patients with dialysis vintage of ≥11 months were treated with RDN (EnligHTN system). Data were obtained on a nondialysis day; at baseline, 1, 3, and 12 months post-RDN.ResultsAt baseline sympathetic neural activation measured by muscle sympathetic nervous activity (MSNA) and plasma norepinephrine concentrations were markedly elevated. Left ventricular hypertrophy (LVH) was evident in 8 of the 9 patients. At 12 months post-RDN, blind analysis revealed that MSNAfrequency (–12.2 bursts/min1, 95% CI [–13.6, –10.7]) and LV mass (–27 g/m2, 95% CI [–47, –8]) were reduced. Mean ambulatory BP (systolic: –24 mm Hg, 95% CI [–42, –5] and diastolic: –13 mm Hg, 95% CI [–22, –4]) was also reduced at 12 months. Office BP was reduced as early as 1 month (systolic: –25 mm Hg, 95% CI [–45, –5] and diastolic: –13 mm Hg, 95% CI [–24, –1]). Both ambulatory and office BP had clinically significant reductions in at least 50% of patients out to 12 months.DiscussionCatheter-based RDN significantly reduced MSNA and LV mass as well as systemic BP in this group of patients with ESKD.

We aimed to develop a metformin dosing strategy to optimise efficacy and safety in patients with reduced kidney function. Metformin data from two studies stratified by kidney function were analysed. The relationship between metformin clearance and kidney function estimates was explored using a regression analysis. The maintenance dose range was predicted at different bands of kidney function to achieve an efficacy target of 1 mg/L for steady-state plasma concentrations. The dosing strategy was evaluated using simulations from a published metformin pharmacokinetic model to determine the probability of concentrations exceeding those associated with lactic acidosis risk, i.e. a steady-state average concentration of 3 mg/L and a maximum (peak) concentration of 5 mg/L. A strong relationship between metformin clearance and estimated kidney function using the Cockcroft and Gault (r2 = 0.699), MDRD (r2 = 0.717) and CKD-Epi (r2 = 0.735) equations was found. The probability of exceeding the safety targets for plasma metformin concentration was <5% for most doses and kidney function levels. The lower dose of 500 mg daily was required to maintain concentrations below the safety limits for patients with an eGFR of 15–29 mL/min. Our analysis suggests that a maximum daily dose of 2250, 1700, 1250, 1000, and 500 in patients with normal kidney function, CKD stage 2, 3a, 3b and 4, respectively, will provide a reasonable probability of achieving efficacy and safety. Our results support the cautious of use metformin at appropriate doses in patients with impaired kidney function.

Given that drug dosing schedules utilise eGFR values as the basis for modifying drug dosing, our results would suggest that a recommendation of a dose reduction according to eGFR alone should be treated with caution.