Altered dietary salt intake for people with chronic kidney disease.

BACKGROUND: Evidence indicates that reducing dietary salt may reduce the incidence of heart disease and delay decline in kidney function in people with chronic kidney disease (CKD). This is an update of a review first published in 2015. OBJECTIVES: To evaluate the benefits and harms of altering dietary salt for adults with CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 6 October 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials comparing two or more levels of salt intake in adults with any stage of CKD. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for eligibility, conducted risk of bias evaluation and evaluated confidence in the evidence using GRADE. Results were summarised using random effects models as risk ratios (RR) for dichotomous outcomes or mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: We included 21 studies (1197 randomised participants), 12 in the earlier stages of CKD (779 randomised participants), seven in dialysis (363 randomised participants) and two in post-transplant (55 randomised participants). Selection bias was low in seven studies, high in one and unclear in 13. Performance and detection biases were low in four studies, high in two, and unclear in 15. Attrition and reporting biases were low in 10 studies, high in three and unclear in eight. Because duration of the included studies was too short (1 to 36 weeks) to test the effect of salt restriction on endpoints such as death, cardiovascular events or CKD progression, changes in salt intake on blood pressure and other secondary risk factors were examined. Reducing salt by mean -73.51 mmol/day (95% CI -92.76 to -54.27), equivalent to 4.2 g or 1690 mg sodium/day, reduced systolic/diastolic blood pressure by -6.91/-3.91 mm Hg (95% CI -8.82 to -4.99/-4.80 to -3.02; 19 studies, 1405 participants; high certainty evidence). Albuminuria was reduced by 36% (95% CI 26 to 44) in six studies, five of which were carried out in people in the earlier stages of CKD (MD -0.44, 95% CI -0.58 to -0.30; 501 participants; high certainty evidence). The evidence is very uncertain about the effect of lower salt intake on weight, as the weight change observed (-1.32 kg, 95% CI -1.94 to -0.70; 12 studies, 759 participants) may have been due to fluid volume, lean tissue, or body fat. Lower salt intake may reduce extracellular fluid volume in the earlier stages of CKD (-0.87 L, 95% CI -1.17 to -0.58; 3 studies; 187 participants; low certainty evidence). The evidence is very uncertain about the effect of lower salt intake on reduction in antihypertensive dose (RR 2.45, 95% CI 0.98 to 6.08; 8 studies; 754 participants). Lower salt intake may lead to  symptomatic hypotension (RR 6.70, 95% CI 2.40 to 18.69; 6 studies; 678 participants; moderate certainty evidence). Data were sparse for other types of adverse events. AUTHORS' CONCLUSIONS: We found high certainty evidence that salt reduction reduced blood pressure in people with CKD, and albuminuria in people with earlier stage CKD in the short-term. If such reductions could be maintained long-term, this effect may translate to clinically significant reductions in CKD progression and cardiovascular events. Research into the long-term effects of sodium-restricted diet for people with CKD is warranted.

Utility of 'back-up' arterio-venous fistulae in patients on peritoneal dialysis and use of haemodialysis catheters.

BACKGROUND: Patients undergoing peritoneal dialysis may require unanticipated transfer to haemodialysis. Back up fistula are often created in selected patients. These may help reduce the infective burden of haemodialysis (HD) catheter. AIM: To study the utility of back-up arterio-venous fistulae (AVF) in patients initiated on peritoneal dialysis (PD) and to determine the rates of HD catheter use in patients requiring conversion to HD. METHODS: Data on HD transfer and HD catheter usage were retrospectively analysed in all patients initiating PD between January 2010 and December 2014 at Royal Adelaide Hospital (RAH; universal back-up AVF creation at PD commencement) and Princess Alexandra Hospital (PAH; selective back-up AVF creation in 'high risk' patients). RESULTS: A total of 374 patients initiated PD during the study period: 142 in RAH group and 232 in PAH group. The groups were reasonably comparable, except that RAH patients were more likely to be older, Caucasian and diabetic. Transfer to HD occurred in 33 (23%) patients in RAH group and 99 (43%) in the PAH group with respective median times to HD transfer of 289 and 295 days. HD catheter usage was required at the time of HD transfer in 11 (33%) patients at RAH and 64 (65%) in patients at PAH (P < 0.001). AVF complications occurred in 13 (9%) patients in RAH group (fistuloplasty n = 8, transposition n = 2, ligation due to ischaemia n = 2 and construction of new AVF n = 1). CONCLUSION: Patients undergoing PD frequently require urgent unanticipated transfer to HD and back-up AVF can be successfully utilised in this setting in the majority of cases, which in turn can reduce the infective burden of HD catheter exposure.

Methamphetamine intoxication and acute kidney injury: A prospective observational case series.

AIM: The effects of methamphetamine intoxication on the kidney are not well reported. We aimed to investigate acute kidney injury (AKI) associated with methamphetamine intoxication, in particular its severity, duration and association with rhabdomyolysis. METHODS: This is a prospective observational series of methamphetamine-intoxicated patients presenting to an Emergency Department. Patients self-reporting recent methamphetamine use, with a positive urine drug screen and an elevated creatinine, were eligible for the study. Urinary neutrophil gelatinase-associated lipocalin (NGAL) was measured, and serum creatinine, creatine kinase and cystatin C concentrations were performed on arrival and at several time points until discharge from hospital. Demographic and clinical data were obtained from the medical records. RESULTS: There were 634 presentations with methamphetamine intoxication over a 10-month period, with 73/595(12%) cases having an elevated serum creatinine concentration on arrival. Fifty presentations in 48 patients were included in the study. Most patients (85%) were male with a median age of 32 years. The median serum creatinine concentration on presentation was 125 µmol/L (IQR:113-135 µmol/L) with 45 (90%) presentations meeting diagnostic criteria for AKI. Concurrent rhabdomyolysis occurred in 22 (44%) presentations with a median CK of 2695 U/L (IQR:1598-5060 U/L). Cystatin C was elevated (> 0.98 mg/L) in 18 cases. An elevated NGAL concentration (>150 µg/L) was present in five (10%) cases. No patients required dialysis. The median length of stay was 19 hours (IQR 14-24 hours). CONCLUSION: AKI is common in methamphetamine intoxication. The kidney injury is relatively mild and short-lived, resolving with crystalloid therapy.

Disseminated cryptococcosis presenting initially as lower limb cellulitis in a renal transplant recipient - a case report.

BACKGROUND: Cellulitis is an unusual presentation of disseminated cryptococcosis, a serious infection seen predominantly in immunocompromised hosts. Disseminated cryptococcosis carries significant morbidity for transplant recipients, especially of the pulmonary and central nervous systems, and carries a high mortality risk. CASE PRESENTATION: We report a 59-year-old renal transplant recipient who presented with bilateral lower leg cellulitis without other symptoms or signs. Failure of conventional therapy for cellulitis prompted a skin biopsy confirming cryptococcal cellulitis. Additional evaluation to exclude disseminated disease revealed Cryptococcus neoformans in blood cultures and cerebrospinal fluid (CSF). Treatment included reduction in immunosuppression regimen and targeted treatment for cryptococcal disease with liposomal amphotericin B and flucytosine followed by fluconazole consolidation and maintenance therapy. Treatment with liposomal amphotericin B and flucytosine followed by fluconazole consolidation and maintenance therapy achieved a good clinical response. Our patient achieved significant reduction in leg cellulitis and recovered without serious complication. CONCLUSIONS: This case suggests that cutaneous cryptococcosis in immunosuppressed patients warrants a low threshold for investigation for disseminated disease even in the absence of other symptoms or signs.

Antimicrobial agents for preventing peritonitis in peritoneal dialysis patients.

BACKGROUND: Peritoneal dialysis (PD) is an important therapy for patients with end-stage kidney disease and is used in more than 200,000 such patients globally. However, its value is often limited by the development of infections such as peritonitis and exit-site and tunnel infections. Multiple strategies have been developed to reduce the risk of peritonitis including antibiotics, topical disinfectants to the exit site and antifungal agents. However, the effectiveness of these strategies has been variable and are based on a small number of randomised controlled trials (RCTs). The optimal preventive strategies to reduce the occurrence of peritonitis remain unclear.This is an update of a Cochrane review first published in 2004. OBJECTIVES: To evaluate the benefits and harms of antimicrobial strategies used to prevent peritonitis in PD patients. SEARCH METHODS: We searched the Cochrane Kidney and Transplant's Specialised Register to 4 October 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: RCTs or quasi-RCTs in patients receiving chronic PD, which evaluated any antimicrobial agents used systemically or locally to prevent peritonitis or exit-site/tunnel infection were included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratio (RR) with 95% confidence intervals (CI). MAIN RESULTS: Thirty-nine studies, randomising 4435 patients, were included. Twenty additional studies have been included in this update. The risk of bias domains were often unclear or high; risk of bias was judged to be low in 19 (49%) studies for random sequence generation, 12 (31%) studies for allocation concealment, 22 (56%) studies for incomplete outcome reporting, and in 12 (31%) studies for selective outcome reporting. Blinding of participants and personnel was considered to be at low risk of bias in 8 (21%) and 10 studies (26%) for blinding of outcome assessors. It should be noted that blinding of participants and personnel was not possible in many of the studies because of the nature of the intervention or control treatment.The use of oral or topical antibiotic compared with placebo/no treatment, had uncertain effects on the risk of exit-site/tunnel infection (3 studies, 191 patients, low quality evidence: RR 0.45, 95% CI 0.19 to 1.04) and the risk of peritonitis (5 studies, 395 patients, low quality evidence: RR 0.82, 95% CI 0.57 to 1.19).The use of nasal antibiotic compared with placebo/no treatment had uncertain effects on the risk of exit-site/tunnel infection (3 studies, 338 patients, low quality evidence: RR 1.34, 95% CI 0.62 to 2.87) and the risk of peritonitis (3 studies, 338 patients, low quality evidence: RR 0.94, 95% CI 0.67 to 1.31).Pre/perioperative intravenous vancomycin compared with no treatment may reduce the risk of early peritonitis (1 study, 177 patients, low quality evidence: RR 0.08, 95% CI 0.01 to 0.61) but has an uncertain effect on the risk of exit-site/tunnel infection (1 study, 177 patients, low quality evidence: RR 0.36, 95% CI 0.10 to 1.32).The use of topical disinfectant compared with standard care or other active treatment (antibiotic or other disinfectant) had uncertain effects on the risk of exit-site/tunnel infection (8 studies, 973 patients, low quality evidence, RR 1.00, 95% CI 0.75 to 1.33) and the risk of peritonitis (6 studies, 853 patients, low quality evidence: RR 0.83, 95% CI 0.65 to 1.06).Antifungal prophylaxis with oral nystatin/fluconazole compared with placebo/no treatment may reduce the risk of fungal peritonitis occurring after a patient has had an antibiotic course (2 studies, 817 patients, low quality evidence: RR 0.28, 95% CI 0.12 to 0.63).No intervention reduced the risk of catheter removal or replacement. Most of the available studies were small and of suboptimal quality. Only six studies enrolled 200 or more patients. AUTHORS' CONCLUSIONS: In this update, we identified limited data from RCTs and quasi-RCTs which evaluated strategies to prevent peritonitis and exit-site/tunnel infections. This review demonstrates that pre/peri-operative intravenous vancomycin may reduce the risk of early peritonitis and that antifungal prophylaxis with oral nystatin or fluconazole reduces the risk of fungal peritonitis following an antibiotic course. However, no other antimicrobial interventions have proven efficacy. In particular, the use of nasal antibiotic to eradicate Staphylococcus aureus, had an uncertain effect on the risk of peritonitis and raises questions about the usefulness of this approach. Given the large number of patients on PD and the importance of peritonitis, the lack of adequately powered and high quality RCTs to inform decision making about strategies to prevent peritonitis is striking.

Recurrent atypical haemolytic uraemic syndrome post kidney transplant due to a CD46 mutation in the setting of SMARCAL1-mediated inherited kidney disease.

Disorders in the regulation of the alternate complement pathway often result in complement-mediated damage to the microvascular endothelium and can be associated with both glomerulonephritis and atypical haemolytic uraemic syndrome. Inherited defects in complement regulatory genes or autoantibodies against complement regulatory proteins are predictive of the severity of the disease and the risk of recurrence post kidney transplantation. Heterozygous mutations in CD46, which codes for a transmembrane cofactor glycoprotein membrane cofactor protein, usually have a lower incidence of end-stage kidney disease and decreased risk of recurrent disease post transplant, as wild-type membrane cofactor protein is present in the transplanted kidney. However, some patients with CD46 mutations have a second variant in other complement regulatory genes increasing the severity of disease. The following case report illustrates the course of a young adult patient with end-stage kidney disease initially ascribed to seronegative systemic lupus erythematosus, who presented with biopsy-proven thrombotic microangiopathy following kidney transplantation. It highlights the complexity associated with disorders of complement regulation and the need for a high index of suspicion and genetic testing in patients who present with thrombotic microangiopathy post-transplant.

Progression of arterial stiffness is associated with changes in bone mineral markers in advanced CKD.

BACKGROUND: Arterial stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease (CKD). There are limited prospective data however on progression of arterial stiffness in CKD, including evaluating associations with bone mineral markers such as fibroblast growth factor 23 (FGF23) and soluble α-klotho (sKl). METHODS: In this prospective, single-center, observational study, arterial stiffness [measured by pulse wave velocity (PWV)] and hormones influencing mineral homeostasis, including serum FGF23 and sKl, were compared between non-dialysis CKD stages 4/5 and healthy controls at baseline and 12 months (12 m). Abdominal aortic calcification (AAC) was quantitated using lateral lumbar radiography at baseline. RESULTS: Forty patients with CKD [mean estimated glomerular filtration rate (eGFR) 19.5 ± 6.7 mL/min/1.73m2] and 42 controls (mean eGFR 88.6 ± 12.9 mL/min/1.73m2) completed follow-up. There were no differences in age, gender and body mass index between groups. A significant increase in FGF23 [240.6 (141.9-1129.8) to 396.8 (160.3-997.7) pg/mL, p = 0.001] was observed in the CKD group but serum phosphate, corrected calcium, parathyroid hormone and sKl did not change significantly over 12 m. At baseline, CKD subjects had higher AAC prevalence [83.8% versus (vs.) 43.6%, p = 0.002] and higher aortic PWV [9.7(7.6-11.7) vs. 8.1 (7.2-9.7) m/s, p = 0.047] compared to controls. At 12 m, aortic PWV increased by 1.3 m/s (95% confidence interval, 0.56 to 2.08, p < 0.001) in the CKD cohort, with 30% of subjects showing progression from normal aortic elasticity to stiffening (PWV > 10 m/s). Serum FGF23 was associated with AAC, abnormal PWV and progression of PWV at 12 m. CONCLUSIONS: Arterial stiffness and serum FGF23, both of which are associated with increased cardiovascular risk, increased over one year in individuals with CKD. Additionally, a significant association was found between serum FGF23 and arterial calcification and stiffness. Larger clinical studies and further experimental work are warranted to delineate the temporal relationship as well as the pathological mechanisms linking FGF23 and vascular disease.

Pro: Meta-analysis: the case for.

With ever-accumulating medical evidence for treatment benefits and harms, it is vital that clinicians are able to access and use up-to-date, best evidence in specific clinical scenarios involving individual patients-the primary goal of evidence-based medicine. In this article, we propose that meta-analysis, when properly conducted and reported in the context of a rigorous systematic review, is an indispensable tool for synthesis and interpretation of clinical evidence for the purpose of informing clinical decision-making by clinicians, patients and health care policy makers. Meta-analysis provides many benefits, including enhanced precision and statistical power, greater transparency, identification of bias, exploration of heterogeneity of effects, enhanced generalizability, efficient integration of clinical knowledge, identification of evidence gaps, better informed future trial design and avoidance of unnecessary research duplication and potential patient harm. The overall standard, clinical value and reach of meta-analysis has been further enhanced by the development of standards for registration, conduct and reporting, as well as advanced meta-analytic techniques, such as network meta-analysis. Of course, meta-analysis can at times be limited by poor quality studies, trial heterogeneity, publication bias and non-rigorous review and analysis, although through appraisal these issues are often able to be identified and explored, such that valuable clinical information can still be obtained. Consequently, meta-analysis is now the most highly cited form of research and is considered by many leading organizations to represent the highest level of clinical evidence. However, to maximize their considerable value, it is essential that all clinicians have the skills to critically appraise, carefully interpret and judiciously apply meta-analyses in their practice.

Assessment of current practice and barriers to antimicrobial prophylaxis in peritoneal dialysis patients.

BACKGROUND: Existing Australasian and international guidelines outline antibiotic and antifungal measures to prevent the development of treatment-related infection in peritoneal dialysis (PD) patients. Practice patterns and rates of PD-related infection vary widely across renal units in Australia and New Zealand and are known to vary significantly from guideline recommendations, resulting in PD technique survival rates that are lower than those achieved in many other countries. The aim of this study was to determine if there is an association between current practice and PD-related infection outcomes and to identify the barriers and enablers to good clinical practice. METHODS: This is a multicentre network study involving eight PD units in Australia and New Zealand, with a focus on adherence to guideline recommendations on antimicrobial prophylaxis in PD patients. Current practice was established by asking the PD unit heads to respond to a short survey about practice/protocols/policies and a 'process map' was constructed following a face-to-face interview with the primary PD nurse at each unit. The perceived barriers/enablers to adherence to the relevant guideline recommendations were obtained from the completion of 'cause and effect' diagrams by the nephrologist and PD nurse at each unit. Data on PD-related infections were obtained for the period 1 January 2011 to 31 December 2011. RESULTS: Perceived barriers that may result in reduced adherence to guideline recommendations included lack of knowledge, procedural lapses, lack of a centralized patient database, patients with non-English speaking background, professional concern about antibiotic resistance, medication cost and the inability of nephrologists and infectious diseases staff to reach consensus on unit protocols. The definitions of PD-related infections used by some units varied from those recommended by the International Society for Peritoneal Dialysis, particularly with exit-site infection (ESI). Wide variations were observed in the rates of ESI (0.06-0.53 episodes per patient-year) and peritonitis (0.31-0.86 episodes per patient-year). CONCLUSIONS: Despite the existence of strongly evidence-based guideline recommendations, there was wide variation in adherence to these recommendations between PD units which might contribute to PD-related infection rates, which varied widely between units. Although individual patient characteristics may account for some of this variability, inconsistencies in the processes of care to prevent infection in PD patients also play a role.

Peritoneal dialysis practice in Australia and New Zealand: A call to sustain the action.

This paper updates a previous 'Call to Action' paper (Nephrology 2011; 16: 19-29) that reviewed key outcome data for Australian and New Zealand peritoneal dialysis patients and made recommendations to improve care. Since its publication, peritonitis rates have improved significantly, although they have plateaued more recently. Peritoneal dialysis patient and technique survival in Australian and New Zealand have also improved, with a reduction in the proportion of technique failures attributed to 'social reasons'. Despite these improvements, technique survival rates overall remain lower than in many other parts of the world. This update includes additional practical recommendations based on published evidence and emerging initiatives to further improve outcomes.

Prevention of peritoneal dialysis-related infections.

The use of peritoneal dialysis (PD) varies widely from country to country, with the main limitation being infectious complications, particularly peritonitis, which leads to technique failure, hospitalization and increased mortality. A large number of prophylactic strategies have been employed to reduce the occurrence of peritonitis, including the use of oral, nasal and topical antibiotics, disinfection of the exit site, modification of the transfer set used in continuous ambulatory PD exchanges, changes to the design of the PD catheter implanted, the surgical method by which the PD catheter is inserted, the type and length of training given to patients, the occurrence of home visits by trained PD nurses, the use of antibiotic prophylaxis in patients undergoing certain invasive procedures and the administration of antifungal prophylaxis to PD patients whenever they are given an antibiotic treatment course. This review summarizes the existing evidence evaluating these interventions to prevent exit-site/tunnel infections and peritonitis.

Altered dietary salt intake for people with chronic kidney disease.

BACKGROUND: Salt intake shows great promise as a modifiable risk factor for reducing heart disease incidence and delaying kidney function decline in people with chronic kidney disease (CKD). However, a clear consensus of the benefits of reducing salt in people with CKD is lacking. OBJECTIVES: This review evaluated the benefits and harms of altering dietary salt intake in people with CKD. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 13 January 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared two or more levels of salt intake in people with any stage of CKD. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for eligibility and conducted risk of bias evaluation. Results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Mean effect sizes were calculated using the random-effects models. MAIN RESULTS: We included eight studies (24 reports, 258 participants). Because duration of the included studies was too short (1 to 26 weeks) to test the effect of salt restriction on endpoints such as mortality, cardiovascular events or CKD progression, changes in salt intake on blood pressure and other secondary risk factors were applied. Three studies were parallel RCTs and five were cross-over studies. Selection bias was low in five studies and unclear in three. Performance and detection biases were low in two studies and unclear in six. Attrition and reporting biases were low in four studies and unclear in four. One study had the potential for high carryover effect; three had high risk of bias from baseline characteristics (change of medication or diet) and two studies were industry funded.There was a significant reduction in 24 hour sodium excretion associated with low salt interventions (range 52 to 141 mmol) (8 studies, 258 participants: MD -105.86 mmol/d, 95% CI -119.20 to -92.51; I(2) = 51%). Reducing salt intake significantly reduced systolic blood pressure (8 studies, 258 participants: MD -8.75 mm Hg, 95% CI -11.33 to -6.16; I(2) = 0%) and diastolic blood pressure (8 studies, 258 participants: MD -3.70 mm Hg, 95% CI -5.09 to -2.30; I(2) = 0%). One study reported restricting salt intake reduced the risk of oedema by 56%. Salt restriction significantly increased plasma renin activity (2 studies, 71 participants: MD 1.08 ng/mL/h, 95% CI 0.51 to 1.65; I(2) = 0%) and serum aldosterone (2 studies, 71 participants: 6.20 ng/dL (95% CI 3.82 to 8.58; I(2) = 0%). Antihypertensive medication dosage was significantly reduced with a low salt diet (2 studies, 52 participants): RR 5.48, 95% CI 1.27 to 23.66; I(2) = 0%). There was no significant difference in eGFR (2 studies, 68 participants: MD -1.14 mL/min/1.73 m(2), 95% CI -4.38 to 2.11; I(2) = 0%), creatinine clearance (3 studies, 85 participants): MD -4.60 mL/min, 95% CI -11.78 to 2.57; I(2) = 0%), serum creatinine (5 studies, 151 participants: MD 5.14 µmol/L, 95% CI -8.98 to 19.26; I(2) = 59%) or body weight (5 studies, 139 participants: MD -1.46 kg; 95% CI -4.55 to 1.64; I(2) = 0%). There was no significant change in total cholesterol in relation to salt restriction (3 studies, 105 participants: MD -0.23 mmol/L, 95% CI -0.57 to 0.10; I(2) = 0%) or symptomatic hypotension (2 studies, 72 participants: RR 6.60, 95% CI 0.77 to 56.55; I(2) = 0%). Salt restriction significantly reduced urinary protein excretion in all studies that reported proteinuria as an outcome, however data could not be meta-analysed. AUTHORS' CONCLUSIONS: We found a critical evidence gap in long-term effects of salt restriction in people with CKD that meant we were unable to determine the direct effects of sodium restriction on primary endpoints such as mortality and progression to end-stage kidney disease (ESKD). We found that salt reduction in people with CKD reduced blood pressure considerably and consistently reduced proteinuria. If such reductions could be maintained long-term, this effect may translate to clinically significant reductions in ESKD incidence and cardiovascular events. Research into the long-term effects of sodium-restricted diet for people with CKD is warranted, as is investigation into adherence to a low salt diet.

A consensus statement on the renal monitoring of Australian patients receiving tenofovir based antiviral therapy for HIV/HBV infection.

A number of antiviral agents used against Human Immunodeficiency Virus (HIV) infection and hepatitis B virus (HBV) mono or co-infection have been associated with real nephrotoxicity (including tenofovir disoproxil fumarate (TDF), atazanavir, indinavir and lopinavir) or apparent changes in renal function (e.g. cobicistat, ritonavir, rilpivirine and dolutegravir). Patients with HIV are at higher risk of acute and chronic renal dysfunction, so baseline assessment and ongoing monitoring of renal function is an important part of routine management of patients with HIV. Given the paucity of evidence in this area, we sought to establish a consensus view on how routine monitoring could be performed in Australian patients on ART regimens, especially those involving TDF. A group of nephrologists and prescribers (an HIV physician and a hepatologist) were assembled by Gilead to discuss practical and reasonable renal management strategies for patients particularly those on TDF-based combination regimens (in the case of those with HIV-infection) or on TDF-monotherapy (in the case of HBV-mono infection). The group considered which investigations should be performed as part of routine practice, their frequency, and when specialist renal referral is warranted. The algorithm presented suggests testing for serum creatinine along with plasma phosphate and an assessment of urinary protein (rather than albumin) and glucose. Here we advocate baseline tests of renal function at initiation of therapy. If creatinine excretion inhibitors (e.g. cobicistat or rilpivirine) are used as part of the ART regimen, we suggest creatinine is rechecked at 4 weeks and this value used as the new baseline. Repeat testing is suggested at 3-monthly intervals for a year and then at least yearly thereafter if no abnormalities are detected. In patients with abnormal baseline results, renal function assessment should be performed at least 6 monthly. In HBV mono-infected patients advocate that a similar testing protocol may be logical.

Human SLC26A1 gene variants: a pilot study.

Kidney stones are a global health problem, incurring massive health costs annually. Why stones recur in many patients remains unknown but likely involves environmental, physiological, and genetic factors. The solute linked carrier (SLC) 26A1 gene has previously been linked to kidney stones in mice. SLC26A1 encodes the sulfate anion transporter 1 (SAT1) protein, and its loss in mice leads to hyperoxaluria and calcium oxalate renal stones. To investigate the possible involvement of SAT1 in human urolithiasis, we screened the SLC26A1 gene in a cohort of 13 individuals with recurrent calcium oxalate urolithiasis, which is the commonest type. DNA sequence analyses showed missense mutations in seven patients: one individual was heterozygous R372H; 4 individuals were heterozygous Q556R; one patient was homozygous Q556R; and one patient with severe nephrocalcinosis (requiring nephrectomy) was homozygous Q556R and heterozygous M132T. The M132 amino acid in human SAT1 is conserved with 15 other species and is located within the third transmembrane domain of the predicted SAT1 protein structure, suggesting that this amino acid may be important for SAT1 function. These initial findings demonstrate genetic variants in SLC26A1 of recurrent stone formers and warrant wider independent studies of SLC26A1 in humans with recurrent calcium oxalate stones.

A randomized controlled trial of oral heme iron polypeptide versus oral iron supplementation for the treatment of anaemia in peritoneal dialysis patients: HEMATOCRIT trial.

BACKGROUND: Preliminary clinical evidence suggests that heme iron polypeptide (HIP) might represent a promising, novel oral iron supplementation strategy in chronic kidney disease. The aim of this multi-centre randomized controlled trial was to determine the ability of HIP administration to augment iron stores in darbepoetin (DPO)-treated patients compared with conventional oral iron supplementation. METHODS: Adult peritoneal dialysis (PD) patients treated with DPO were randomized 1:1 to receive two capsules daily of either HIP or ferrous sulphate per os for 6 months. The primary outcome measure was transferrin saturation (TSAT). Secondary outcomes comprised serum ferritin, haemoglobin, DPO dose and responsiveness, and adverse events. RESULTS: Sixty-two patients were randomized to HIP (n = 32) or ferrous sulphate (n = 30). On intention-to-treat analysis, the median (inter-quartile range) TSAT was 22% (16-29) in the HIP group compared with 20% (17-26) in controls (P = 0.65). HIP treatment was not significantly associated with TSAT at 6 months on multivariable analysis (P = 0.95). Similar results were found on per-protocol analysis and subgroup analysis in iron-deficient patients. Serum ferritin levels at 6 months were significantly lower in the HIP group (P = 0.003), while the cost of HIP was 7-fold higher than that of ferrous sulphate. No other differences in secondary outcomes were observed. CONCLUSIONS: HIP showed no clear safety or efficacy benefit in PD patients compared with conventional oral iron supplements. The reduction in serum ferritin levels and high costs associated with HIP therapy suggest that this agent is unlikely to have a significant role in iron supplementation in PD patients.

Changes in serum prolactin, sex hormones and thyroid function with alternate nightly nocturnal home haemodialysis.

AIM: Uraemia is associated with hyperprolactinaemia, low total (TT) and free (FT) serum testosterone, high luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and, in women, anovulatory cycles and premature menopause. We hypothesize that extended hours haemodialysis may improve these derangements. METHODS: This is an observational cohort study of 30 men (age 54±13 years, body mass index (BMI) 28.1±5.8 kg/m2) and seven women (age 41±11 years, BMI 32.2±11.2 kg/m2) established on chronic home haemodialysis (3-5 h, 3.5-5 sessions weekly) who were converted to nocturnal home haemodialysis (6-9 h, 3.5-5 sessions weekly). Serum was collected at baseline and 6 months for measurement of TT, sex hormone binding globulin (SHBG), LH, FSH, prolactin, thyroid-stimulating hormone and thyroxine. RESULTS: In the male patients (n=25), serum prolactin significantly fell (281 (209.5-520) vs 243 (187-359) mU/L, P=0.001) and TT (12.6±5.8 vs 15.2±8.1 nmol/L, P=0.06) and FT (281±118 vs 359±221 pmol/L, P=0.01) increased. SHBG, LH and FSH were unchanged. At 6 months, two of the three women under 40 years of age had return of regular menses after being amenorrhoeic or having prolonged and irregular menses at baseline. There were insufficient women in this study to further analyse changes in sex hormone levels. Thyroid function tests remained stable. CONCLUSION: Alternate nightly nocturnal haemodialysis significantly improves hyperprolactinaemia and hypotestosteronaemia in men. Menstrual cycling may be re-established in young women. The effect of these changes on fertility has not been established. Patients should be counselled about the possibility of increased fertility before conversion to extended hours haemodialysis regimens.

Peritoneal dialysis practice in Australia and New Zealand: a call to action.

Peritoneal dialysis technique survival in Australia and New Zealand is lower than in other parts of the world. More than two-thirds of technique failures are related to infective complications (predominantly peritonitis) and 'social reasons'. Practice patterns vary widely and more than one-third of peritoneal dialysis units do not meet the International Society of Peritoneal Dialysis minimum accepted peritonitis rate. In many cases, poor peritonitis outcomes reflect significant deviations from international guidelines. In this paper we propose a series of practical recommendations to improve outcomes in peritoneal dialysis patients through appropriate patient selection, prophylaxis and treatment of infectious complications, investigation of social causes of technique failure and a greater focus on patient education and clinical governance.