142 Summary of Recommendation Statements 143 Chapter 1: Introduction 154 Chapter 2: General principles in the management of glomerular disease 156 Chapter 3: Steroid-sensitive nephrotic syndrome in children 163 Chapter 4: Steroid-resistant nephrotic syndrome in children 172 Chapter 5: Minimal-change disease in adults 177 Chapter 6: Idiopathic focal segmental glomerulosclerosis in adults 181 Chapter 7: Idiopathic membranous nephropathy 186 Chapter 8: Idiopathic membranoproliferative glomerulonephritis 198 Chapter 9: Infection-related glomerulonephritis 200 Chapter 10: Immunoglobulin A nephropathy 209 Chapter 11: Henoch-Schönlein purpura nephritis 218 Chapter 12: Lupus nephritis 221 Chapter 13: Pauci-immune focal and segmental necrotizing glomerulonephritis 233 Chapter 14: Anti-glomerular basement membrane antibody glomerulonephritis 240 Methods for guideline development 243 Biographic and Disclosure Information 252

KDIGO Clinical Practice Guideline for Glomerulonephritis

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have well-known gastrointestinal and renal toxic reactions. Effects of NSAIDs on blood pressure are less appreciated. A meta-analysis was performed to determine the hypertensive effects of NSAIDs and rank them by magnitude of change in mean arterial pressure (MAP). Methods: A literature search of published English-language studies of NSAIDs and their effects on blood pressure was done. Studies were included if they met the following criteria: (1) the studies were intervention studies; (2) NSAIDs at any dose or aspirin at doses of 1.5 g/d or greater were included; (3) documentation of blood pressure was provided; and (4) the studies were 24 hours in duration. Studies were excluded if 20% or more of their participants dropped out or if the dose of antihypertensive drugs was adjusted while the subjects were taking NSAIDs. The major outcome was change in MAP while patients were receiving NSAIDs. Each NSAID arm was extracted from its trial. Information on possible confounders, including subject age, trial quality, amount of dietary salt intake, and whether study subjects were hypertensive or normotensive, was recorded. We calculated the average change in MAP on each NSAID, adjusting for confounders. Results: Fifty-four studies with 123 NSAID treatment arms met inclusion criteria. The mean age of subjects was 46 years. Of the 1324 participants, 1213 subjects (92%) were hypertensive. The effects of NSAIDs on blood pressure were found solely in hypertensive subjects. Among these, the increase in MAP after adjusting for amount of dietary salt intake was 3.59 mm Hg for indomethacin (57 treatment arms), 3.74 mm Hg for naproxen (four arms), and 0.49 mm Hg for piroxicam (four arms). The MAP decreased by 2.59 mm Hg for placebo (10 arms), 0.83 mm Hg for ibuprofen (six arms), 1.76 mm Hg for aspirin (four arms), and 0.16 mm Hg for sulindac (23 arms). The effects on MAP by using placebo, sulindac, and aspirin were statistically significantly different from indomethacin. Conclusions: In short-term use, NSAIDs vary considerably in their effect on blood pressure. Of the drugs studied, indomethacin and naproxen were associated with the largest increases in blood pressure. The average effects of piroxicam, aspirin, ibuprofen, and sulindac were negligible. (Arch Intern Med. 1993;153:477-484)

A Meta-analysis of the Effects of Nonsteroidal Anti-inflammatory Drugs on Blood Pressure

https://www.ajkd.org/article/S0272-6386(13)00903-7/pdf

KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for Glomerulonephritis

Background: Although many studies have examined the effects of antihypertensive agents on proteinuria and glomerular filtration rate in patients with kidney disease, many questions remain unresolved. These questions include whether the effects of agents differ, whether their effects are similar in diabetic and nondiabetic patients with renal disease, and whether the effects of any agents are independent of blood pressure reductions. Methods: We conducted a meta-analysis of studies obtained with MEDLINE and bibliographies from comprehensive reviews but included only investigations with follow-up times of at least 6 months. We combined data (1) in an analysis of randomized controlled trials, (2) in a separate univariate analysis of controlled and uncontrolled trials, and (3) using weighted multiple linear regression. Results: In 14 randomized controlled trials, angiotensin-converting enzyme inhibitors caused a greater decrease in proteinuria (pooled mean [95% confidence intervals], -0.51 [-0.68 to -0.35],In [treatment/control]), improvement in glomerular filtration rate (0.13 mL/min per month [0.10 to 0.16 mL/min per month]), and decline in mean arterial pressure (-4.0 mm Hg [-4.9 to -3.0 mm Hg]) compared with controls. In a multivariate analysis of controlled and uncontrolled trials, each 10—mm Hg reduction in blood pressure decreased proteinuria (regression coefficient [95% confidence interval] -0.14 [-0.22 to -0.06] In [after/before]), but angiotensin-converting enzyme inhibitors (-0.45 [-0.58 to -0.32]) and nondihydropyridine calcium antagonists (-0.38 [-0.70 to -0.06]) were associated with additional declines in proteinuria that were independent of blood pressure changes and diabetes. Each 10—mm Hg reduction in blood pressure caused a relative improvement in glomerular filtration rate (0.18 mL/min per month [0.04 to 0.31 mL/min per month]), but among diabetic patients there was a tendency for dihydropyridine calcium antagonists to cause a relative reduction in glomerular filtration rate (-0.68 mL/min per month [-1.31 to -0.04 mL/min per month]). Conclusions: Long-term beneficial effects of antihypertensive agents on proteinuria and glomerular filtration rate are proportional to blood pressure reductions and are similar in diabetic and nondiabetic patients with renal disease. In addition, angiotensin-converting enzyme inhibitors, and possibly nondihydropyridine calcium antagonists, have additional beneficial effects on proteinuria that are independent of blood pressure reductions. (Arch Intern Med. 1995;155:1073-1080)

Long-term Effects of Antihypertensive Agents on Proteinuria and Renal Function

Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal diseases. Endothelial dysfunction, in response to a number of risk factors or injury such as hypertension, diabetes mellitus, hypercholesteremia, and cigarette smoking, disrupts the balance of vasodilation and vasoconstriction, vascular smooth muscle cell growth, the inflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have deleterious effects on the heart, vasculature, and the kidneys. The imbalance resulting from increased local formation of angiotensin II and increased bradykinin degradation favors cardiovascular disease. Indeed, ACE inhibitors effectively reduce high blood pressure and exert cardio- and renoprotective actions. Recent evidence suggests that a principal target of ACE inhibitor action is at the tissue sites. Pharmacokinetic properties of various ACE inhibitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensives (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the significance of these drug differences and their impact on clinical events.

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The relevance of tissue angiotensin-converting enzyme: Manifestations in mechanistic and endpoint data

Recent experimental and clinical data have suggested that angiotension converting enzyme (ACE) inhibitors may decrease glomerular proteinuria by specific effects on the glomerulus. We studied a group of 15 adult patients with chronic renal failure and proteinuria due to various glomerulopathies. These patients had mild to moderate hypertension which was effectively controlled with conventional antihypertensive therapy. We then treated the patients with captopril, maintaining a similar dietary protein and salt intake. After 6 months of study, proteinuria was reduced significantly without reduction in inulin or para-aminohippurate clearance. This supports the concept that captopril may have salutary effects on the glomerulus, independently of its effect on systemic blood pressure.

Control of hypertension with the angiotensin converting enzyme inhibitor captopril reduces glomerular proteinuria.

A 12-year-old boy presented with acute renal failure (ARF) accompanied by a disproportionate increase of serum uric acid level and massive uric acid crystalluria. After alkalinization and allopurinol therapy, serum uric acid and renal function returned to normal values. A further enzymatic study showed the existence of a partial hypoxanthine-guanine phosphoribosyl transferase (HPRT) deficit (less than 1% of HPRT normal activity). Although ARF is an exceptional form of presentation of HPRT deficiency, this possibility should be considered whenever an ARF is accompanied by disproportionate high levels of serum uric acid.

Partial deficit of hypoxanthine guanine phosphoribosyl transferase presenting as acute renal failure.

In a group of 26 patients diagnosed as essential hypertensive (EH) and in a control group (CG) of 27 normotensive volunteers the urinary excretion of PGE2, plasma renin activity (PRA) and plasma aldosterone were measured. EH patients were classified into normoreninemic (NREH) (n=21) and hyporeninemic(LREH) (n=5) by the response of PRA to the combined stimuli of ambulation and furosemide. Urinary PGE2 excretion was higher in NREH than in CG (p<0.05) while LREH showed values lower than in CG(p<0.001). Plasma aldosterone levels were similar in the three groups. In CG and EH patients PRA and urinary PGE2 were closely related (CG r=0.516, p<0.05, EH patients r=0.674, p<0.001).Indomethacin administration induced a decrease of PGE2 in both CG (n=8) and NREH (n=8) (p<0.01). In contrast, indomethacin induced no changes in PGE2 excretion of LREH (n=5). Furthermore in the group of patients with NREH indomethacin induced a significant increase in blood pressure (p<0.01) and body weight (p<0.01) while glomerular filtr...

The role of urinary PGE2 and renin-angiotensin-aldosterone system in the pathogenesis of essential hypertension.

We have prospectively investigated the effect of desferrioxamine (DFO) administration (2 gi.v. after every haemodialysis session for 6 months) on the normocytic and normochromic anaemia of seven haemodialysis patients. None had either clinical or analytical data characteristic of chronic aluminium intoxication. At the end of DFO therapy, the haematocrit had increased from 20.5 +/- 2.7% to 30.4 +/- 7.7% (P less than 0.005), and the transfusional requirements decreased from 3.5 +/- 2.2 units (range 1-8 units) in the 6 months prior to DFO, to 0.7 +/- 0.9 units (range 0-2 units) during DFO administration (P less than 0.01). No transfusion was required during the second half of the DFO therapy period. Serum ferritin decreased from 105g +/- 532 nmol/l (2649 +/- 1331 ng/ml) to 507 +/- 403 nmol/l (1268 +/- 1008 ng/ml) (P less than 0.025). Two months after DFO withdrawal the haematocrit value fell significantly to 22.2 +/- 1.6% (P less than 0.01). DFO therapy was restarted in one patient at a lower dose (1 gi.v. after every haemodialysis session) and an increase of haematocrit from 23.8% to 40.2% was again observed after 3 months of treatment. The tolerance to DFO was excellent. We conclude that DFO therapy should be considered in haemodialysis patients with severe anaemia and increased blood transfusion requirements.

Improvement of Anaemia With Desferrioxamine in Haemodialysis Patients

We report a case of minimal change nephrotic syndrome in which acute renal function derangement developed in the absence of any precipitating factor. Histological signs of tubular necrosis were evident

Millet Vg

Papers

Control of hypertension with the angiotensin converting enzyme inhibitor captopril reduces glomerular proteinuria.

Partial deficit of hypoxanthine guanine phosphoribosyl transferase presenting as acute renal failure.

The role of urinary PGE2 and renin-angiotensin-aldosterone system in the pathogenesis of essential hypertension.

Improvement of Anaemia With Desferrioxamine in Haemodialysis Patients

Acute Renal Failure and Tubular Dysfunction Associated with Minimal Change Nephrotic Syndrome