Pelvic floor reconstruction following gynecologic exenterative surgery.

At the end of exenterative procedures, the problem of bowel placement in the pelvic cavity denuded of peritoneum is still one of the most taxing and potentially troublesome problems of radical pelvic surgery. A technic which utilizes pelvic peritoneum to form a complete peritoneal diaphragm between the abdominal and pelvic cavities is described. Experience with this technic is with a small personal series of 15 patients which is presented

Acidemia alone does not stimulate rat renal Na+-H+ antiporter activity

To examine whether systemic acidemia is the cause of the adaptive increase in renal brush-border membrane (BBM) Na+-H+ exchange activity seen in metabolic acidosis, we examined the time course of changes in Na+-H+ exchange activity in rats with chronic metabolic or respiratory acidosis. Metabolic acidosis was created by allowing rats free access to a 1.5% NH4Cl drinking solution. Respiratory acidosis was created by housing rats in a chamber designed to maintain ambient PCO2 levels at 10%. All rats were fed normal rat chow. Control and respiratory acidosis rats had free access to tap water. Rats from each group were studied 1, 3, 5, 7, and 14 days after onset of treatment. Na+-H+ exchange activity was examined in renal BBM vesicles using acridine orange. In both metabolic acidosis and respiratory acidosis, arterial blood [H+] increased markedly at day 1 and returned toward normal thereafter; at day 14, [H+] was elevated to a comparable degree in both groups. In metabolic acidosis, Na+-H+ exchange activity remained at control levels for 3 days but increased markedly thereafter. In contrast, in respiratory acidosis no adaptive increase in activity occurred at any time. Because no correlation was found between blood [H+] and renal BBM Na+-H+ exchange activity, we conclude that stimuli other than systemic acidemia are responsible for the adaptation seen in chronic metabolic acidosis. </jats:p

The remission clinic approach to halt the progression of kidney disease

Randomized multicenter studies in diabetic and nondiabetic patients with chronic proteinuric nephropathies have clearly demonstrated that renin-angiotensin system (RAS) inhibitors, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) used alone or in combination, effectively retard renal disease progression. Proteinuria reduction, in addition to arterial blood pressure control, largely mediates the nephroprotective effect of RAS inhibitor therapy. Despite RAS inhibition, however, most patients with chronic kidney disease (CKD) progress to end-stage renal disease (ESRD). This highlights the importance of innovative therapies to halt or revert CKD progression in those at risk. Along this line, a multimodal strategy (Remission Clinic) targeting urinary proteins by dual RAS inhibition with ACE inhibitors and ARBs up-titrated to maximum tolerated doses, by intensified blood pressure control, amelioration of dyslipidemia by statins, smoking cessation and healthy lifestyle implementation was safely and effectively applied at our outpatient clinic to normalize urinary proteins and prevent renal function loss in patients otherwise predicted to rapidly progress to ESRD because of nephrotic-range proteinuria refractory to standard antihypertensive dosages of an ACE inhibitor. This approach achieved remission or regression of proteinuria and stabilized kidney function in most cases, and almost fully prevented progression to ESRD. Provided patients are closely monitored and treatment is cautiously up-titrated according to tolerability, this approach might be safely applied in day-by-day hospital practice. Effective prevention of ESRD would reduce costs of renal replacement therapy by dialysis or transplantation and would be life-saving where these are not available for all patients in need

Effects of Sevelamer Carbonate in Patients With CKD and Proteinuria: The ANSWER Randomized Trial

Rationale &amp; Objective: Hyperphosphatemia is associated with increased risk for chronic kidney disease (CKD) progression and reduced antiproteinuric effects of renin-angiotensin system (RAS) blockers. We investigated whether the phosphate binder sevelamer carbonate may enhance the antiproteinuric effect of RAS inhibitors in patients with CKD. Study Design: Phase 2, randomized, controlled, open-label, crossover trial. Setting &amp; Participants: Between November 2013 and December 2014, we enrolled 53 patients with CKD with estimated glomerular filtration rates (eGFRs) &gt; 15 mL/min/1.73 m 2 and residual proteinuria with protein excretion 65 0.5 g/24 h despite maximal tolerated ramipril and/or irbesartan therapy from 2 nephrology units in Italy. Intervention: After stratification by serum phosphate level, 644 or &gt;4 mg/dL, patients were randomly assigned to 3 months of sevelamer (1,600 mg thrice daily) treatment followed by 3 months without sevelamer separated by a 1-month washout period or 3 months without sevelamer followed by 3 months with sevelamer, also separated by a 1-month washout period. Outcomes: The primary outcome was 24-hour proteinuria (n = 49 patients). Secondary outcomes included measured GFR (using iohexol plasma clearance), office blood pressure (BP), serum lipid levels, levels of inflammation and bone metabolism biomarkers, urinary electrolyte levels, and arterial stiffness. Results: Changes in proteinuria during the 3-month treatment with (from 1.36 [IQR, 0.77-2.51] to 1.36 [IQR, 0.77-2.60] g/24 h) or without (from 1.36 [IQR, 0.99-2.38] to 1.48 [IQR, 0.81-2.77] g/24 h) sevelamer were similar (P = 0.1). Sevelamer reduced urinary phosphate excretion without affecting serum phosphate levels. Sevelamer reduced C-reactive protein (CRP), glycated hemoglobin, and total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol levels without affecting levels of office BP, measured GFR, fibroblast growth factor 23, klotho, intact parathyroid hormone, serum vitamin D, or other urinary electrolytes. Results were similar in the low- and high-phosphate groups. Sevelamer was well tolerated. Adverse events were comparable between treatment periods. One case of transient hypophosphatemia was observed during treatment with sevelamer. Limitations: Short treatment duration, lower pretreatment proteinuria than expected. Conclusions: 3-month sevelamer treatment did not reduce proteinuria in patients with CKD on maximal RAS blockade. Amelioration of inflammation and dyslipidemia with sevelamer treatment raises the possibility that it may confer benefit in patients with CKD beyond reduction of proteinuria. Funding: Sanofi (Milan, Italy). Trial Registration: Registered at ClinicalTrials.gov with study number NCT01968759

Effects of sevelamer carbonate in patients with ckd and proteinuria. the answer randomized trial

Rationale &amp; Objective: Hyperphosphatemia is associated with increased risk for chronic kidney disease (CKD) progression and reduced antiproteinuric effects of renin-angiotensin system (RAS) blockers. We investigated whether the phosphate binder sevelamer carbonate may enhance the antiproteinuric effect of RAS inhibitors in patients with CKD. Study Design: Phase 2, randomized, controlled, open-label, crossover trial. Setting &amp; Participants: Between November 2013 and December 2014, we enrolled 53 patients with CKD with estimated glomerular filtration rates (eGFRs) &gt; 15 mL/min/1.73 m2 and residual proteinuria with protein excretion ≥ 0.5 g/24 h despite maximal tolerated ramipril and/or irbesartan therapy from 2 nephrology units in Italy. Intervention: After stratification by serum phosphate level, ≤4 or &gt;4 mg/dL, patients were randomly assigned to 3 months of sevelamer (1,600 mg thrice daily) treatment followed by 3 months without sevelamer separated by a 1-month washout period or 3 months without sevelamer followed by 3 months with sevelamer, also separated by a 1-month washout period. Outcomes: The primary outcome was 24-hour proteinuria (n = 49 patients). Secondary outcomes included measured GFR (using iohexol plasma clearance), office blood pressure (BP), serum lipid levels, levels of inflammation and bone metabolism biomarkers, urinary electrolyte levels, and arterial stiffness. Results: Changes in proteinuria during the 3-month treatment with (from 1.36 [IQR, 0.77-2.51] to 1.36 [IQR, 0.77-2.60] g/24 h) or without (from 1.36 [IQR, 0.99-2.38] to 1.48 [IQR, 0.81-2.77] g/24 h) sevelamer were similar (P = 0.1). Sevelamer reduced urinary phosphate excretion without affecting serum phosphate levels. Sevelamer reduced C-reactive protein (CRP), glycated hemoglobin, and total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol levels without affecting levels of office BP, measured GFR, fibroblast growth factor 23, klotho, intact parathyroid hormone, serum vitamin D, or other urinary electrolytes. Results were similar in the low- and high-phosphate groups. Sevelamer was well tolerated. Adverse events were comparable between treatment periods. One case of transient hypophosphatemia was observed during treatment with sevelamer. Limitations: Short treatment duration, lower pretreatment proteinuria than expected. Conclusions: 3-month sevelamer treatment did not reduce proteinuria in patients with CKD on maximal RAS blockade. Amelioration of inflammation and dyslipidemia with sevelamer treatment raises the possibility that it may confer benefit in patients with CKD beyond reduction of proteinuria. Funding: Sanofi (Milan, Italy). Trial Registration: Registered at ClinicalTrials.gov with study number NCT01968759