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Background Baseline serum creatinine (bSCr) is required for diagnosing acute kidney injury (AKI). In children, bSCr is commonly defined as the lowest measurement within 3 months of admission. Measured values are often missing and estimating bSCr using height-based glomerular filtration rate (GFR) equations is problematic when height is unavailable. Methods This is a retrospective cohort study including 538 children admitted to the intensive care unit (ICU) between 2003 and 2005 at two centers in Canada, with measured bSCr, height, and ICU-SCr values. We evaluated the bias, accuracy, and precision of back-calculating bSCr from height-dependent and height-independent GFR equations. Agreement of AKI defined using measured and estimated bSCr was calculated. Multivariate analyses were performed to assess the impact of bSCr estimation methods on the association between AKI and ICU mortality, length of stay, and duration of mechanical ventilation. Results Both methods underestimated bSCr by 1-3%, showed good accuracy (~30% of patients with estimated bSCr within 10% of measured bSCr), but poor precision (wide 95% limits of agreement). The agreement between AKI defined by estimated versus measured bSCr was >80% ([kappa] >0.5). The height-independent method performed best in children >13 years old; however, overall, both methods performed similarly across age subgroups. AKI was associated with longer stay, prolonged mechanical ventilation, and ICU mortality using measured and estimated bSCr. Conclusions Height-dependent and height-independent bSCr estimation methods were comparable. This may have significant implications for performing pediatric AKI research using large databases, and in clinical care to define AKI when height is unknown., Author(s): Erin Hessey [sup.1] , Rami Ali [sup.2] [sup.3] , Marc Dorais [sup.4] , Geneviève Morissette [sup.5] , Michael Pizzi [sup.1] , Nikki Rink [sup.7] , Philippe Jouvet [sup.6] , [...]

Background Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetically determined renal disease. In affected patients, renal function may progressively decline up to end-stage renal disease (ESRD), and approximately 10% of those with ESRD are affected by ADPKD. The somatostatin analog octreotide long-acting release (octreotide-LAR) slows renal function deterioration in patients in early stages of the disease. We evaluated the renoprotective effect of octreotide-LAR in ADPKD patients at high risk of ESRD because of later-stage ADPKD. Methods and findings We did an internally funded, parallel-group, double-blind, placebo-controlled phase III trial to assess octreotide-LAR in adults with ADPKD with glomerular filtration rate (GFR) 15-40 ml/min/1.73 m.sup.2 . Participants were randomized to receive 2 intramuscular injections of 20 mg octreotide-LAR (n = 51) or 0.9% sodium chloride solution (placebo; n = 49) every 28 days for 3 years. Central randomization was 1:1 using a computerized list stratified by center and presence or absence of diabetes or proteinuria. Co-primary short- and long-term outcomes were 1-year total kidney volume (TKV) (computed tomography scan) growth and 3-year GFR (iohexol plasma clearance) decline. Analyses were by modified intention-to-treat. Patients were recruited from 4 Italian nephrology units between October 11, 2011, and March 20, 2014, and followed up to April 14, 2017. Baseline characteristics were similar between groups. Compared to placebo, octreotide-LAR reduced median (95% CI) TKV growth from baseline by 96.8 (10.8 to 182.7) ml at 1 year (p = 0.027) and 422.6 (150.3 to 695.0) ml at 3 years (p = 0.002). Reduction in the median (95% CI) rate of GFR decline (0.56 [-0.63 to 1.75] ml/min/1.73 m.sup.2 per year) was not significant (p = 0.295). TKV analyses were adjusted for age, sex, and baseline TKV. Over a median (IQR) 36 (24 to 37) months of follow-up, 9 patients on octreotide-LAR and 21 patients on placebo progressed to a doubling of serum creatinine or ESRD (composite endpoint) (hazard ratio [HR] [95% CI] adjusted for age, sex, baseline serum creatinine, and baseline TKV: 0.307 [0.127 to 0.742], p = 0.009). One composite endpoint was prevented for every 4 treated patients. Among 63 patients with chronic kidney disease (CKD) stage 4, 3 on octreotide-LAR and 8 on placebo progressed to ESRD (adjusted HR [95% CI]: 0.121 [0.017 to 0.866], p = 0.036). Three patients on placebo had a serious renal cyst rupture/infection and 1 patient had a serious urinary tract infection/obstruction, versus 1 patient on octreotide-LAR with a serious renal cyst infection. The main study limitation was the small sample size. Conclusions In this study we observed that in later-stage ADPKD, octreotide-LAR slowed kidney growth and delayed progression to ESRD, in particular in CKD stage 4. Trial registration ClinicalTrials.gov NCT01377246; EudraCT: 2011-000138-12., Author(s): Norberto Perico 1, Piero Ruggenenti 1,2,*, Annalisa Perna 1, Anna Caroli 1, Matias Trillini 1, Sandro Sironi 3,4, Antonio Pisani 5, Eleonora Riccio 5, Massimo Imbriaco 6, Mauro Dugo [...]

Background No adequate statistical model has been established to estimate future glomerular filtration rate (GFR) in children after kidney transplantation (KTX). Equations based on simple linear regression analysis as used in adults are not established in children. Methods An optimal prognostic model of GFR was generated for 63 children at 3-7 years after KTX. The main regression model for prediction of the log-transformed GFR (logGFR) included the mean monthly change of GFR in the period 3-24 months after KTX (AGFR), the baseline GFR at 3 months (bGFR), and an intercept. Additionally, we investigated if the inclusion of cofactors leads to more precise predictions. The model was validated by leave-one-out cross-validation for years 3-7 after KTX. Prognostic quality was determined with the mean squared error (MSE) and mean absolute error (MAE). Results were compared with the simple linear regression model used in adults. Results The following statistical model was calculated for every prognosis year (i = 3, 7): log([GFR.sub.i]) = [β.sub.i0] + [β.sub.i1] x ΔGFR + [β.sub.i2] X bGFR Comparison of the new statistical model and the simple linear model for adults led to relevantly lower MSEs and MAEs for the new model (year 7: New model: MSE 0.1, MAE 0.3/adult model: MSE 1069, MAE 18). The benefit of inclusion of cofactors was not relevant. Conclusions This statistical model is able to predict long-term graft function in children with very high precision. Keywords Glomerular filtration rate . Pediatric . Kidney transplantation, Introduction At present, the 1- and 5-year graft survival rates in pediatric kidney transplantation (KTX) are 95 and 85 %, respectively for living donations, and 93 and 77 %, respectively, [...]

Background Limited data exist on the performance of cystatin C-based glomerular filtration rate (GFR) equations in pediatric transplant recipients and other high-risk patients. The aim of our study was therefore to evaluate the performance of current cystatin C-based equations in this population. Methods This was a retrospective, cross-sectional study of 141 consecutive patients (58 % post-transplant) who received a nuclear medicine GFR (NucGFR) examination using [sup.99m]Tc-diethylenetriaminepentaacetic acid at our institution. Subjects included children receiving liver, kidney or hematopoietic stem cell transplants and patients with oncologic or urologic disease. GFR estimates using published GFR estimating equations, including those based on cystatin C (Filler, Zappitelli, Larsson, Hoek, Rule and Le Bricon equations, respectively) and on both cystatin C and creatinine (Zappitelli, Bouvet and Schwartz equations, respectively), were evaluated and compared to the NucGFR measurement using Bland-Altman analysis. Results The mean NucGFR was 95 (interquartile range 76111) ml/min/1.73 [m.sup.2]. Of the cystatin C-based equations, the Rule, Hoek, Zappitelli and Schwartz (2009 CKiD equation) formulas provided the closest agreement to the NucGFR estimate. All other formulas overestimated the GFR in our cohort. Conclusion Cystatin C-based GFR formulas can provide an accurate estimation of NucGFR in a pediatric population with a high proportion of transplant recipients and oncology patients. Keywords Cystatin C * Glomerular filtration rate * Transplant * Oncology * Pediatrics, Introduction Accurate assessment of kidney function is essential in the care of children at high risk for renal injury and chronic kidney disease (CKD), such as those receiving a transplant. [...]

BACKGROUND: Cadmium is a nephrotoxicant at high exposure levels. Few studies have evaluated the role of cadmium in kidney function at low-exposure levels. OBJECTIVE: We evaluated the association of blood [...]

In vitro experiments showed that the connecting tubule (CNT) sends a signal that dilates the afferent arteriole (Af-Art) when [Na.sup.+] reabsorption in the CNT lumen increases. We call this process CNT glomerular feedback (CTGF) to differentiate it from tubuloglomerular feedback (TGF), which is a cross talk between the macula densa (MD) and the Af-Art. In TGF, the MD signals the Af-Art to constrict when NaC1 transport by the MD is enhanced by increased luminal NaCI. CTGF is mediated by CNT [Na.sup.+] transport via epithelial [Na.sup.+] channels (ENaC). However, we do not know whether CTGF occurs in vivo or whether it opposes the increase in Af-Art resistance caused by TGF. We hypothesized that CTGF occurs in vivo and opposes TGF. To test our hypothesis, we conducted in vivo micropuncture of individual rat nephrons, measuring stop-flow pressure ([P.sub.SF]) as an index of glomerular filtration pressure. To test whether activation of CTGF opposes TGF, we used benzamil to block CNT [Na.sup.+] transport and thus CTGF. CTGF inhibition with the ENaC blocker benzamil (1 [micro]M) potentiated the decrease in [P.sub.SF] at 40 and 80 nl/min. Next, we tested whether we could augment CTGF by inhibiting NaC1 reabsorption in the distal convoluted tubule with hydrochlorothiazide (HCTZ, 1 mM) to enhance NaC1 delivery to the CNT. In the presence of HCTZ, benzamil potentiated the decrease in [P.sub.SF] at 20, 40, and 80 nl/min. We concluded that in vivo CTGF occurs and opposes the vasoconstrictor effect of TGF. afferent arteriole; macula densa; connecting tubule; glomerular filtration rate; sodium ion transport; benzamil; stop-flow pressure doi: 10.1152/ajprenal.00403.2010

A study was conducted to evaluate the impact of timing of dialysis as a form of treatment in the case of patients with stage V chronic kidney disease. Results indicated that early dialysis did not result in improved survival rates or improved outcomes in the case of such patients as compared to late dialysis.

Contag SA, Bi J, Chappell MC, Rose JC. Developmental effect of antenatal exposure to betamethasone on renal angiotensin H activity in the young adult sheep. Am J Physiol Renal Physiol 298: F847-F856, 2010. First published January 13, 2010; doi:10.1152/ajprenal.00497.2009.--Antenatal corticosteroids may have long-term effects on renal development which have not been clearly defined. Our objective was to compare the responses to intrarenal infusions of ANG II in two groups of year-old, male sheep: one group exposed to a clinically relevant dose of betamethasone before birth and one not exposed. We wished to test the hypothesis that antenatal steroid exposure would enhance renal responses to ANG II in adult life. Six pairs of male sheep underwent unilateral nephrectomy and renal artery catheter placement. The sheep were infused for 24 h with ANG II or with ANG II accompanied by blockade of the angiotensin type 1 (A[T.sub.1]) or type 2 (AT2) receptor. Baseline mean arterial blood pressure among betamethasone-exposed sheep was higher than in control animals (85.8 [+ or -] 2.2 and 78.3 [+ or -] 1.0 mmHg, respectively, P = 0.003). Intrarenal infusion of ANG II did not increase systemic blood pressure (P [greater than or equal to] 0.05) but significantly decreased effective renal plasma flow and increased renal artery resistance (P < 0.05). The decrease in flow and increase in resistance were significantly greater in betamethasone- compared with vehicleexposed sheep (betamethasone P < 0.05, vehicle P [greater than or equal to] 0.05). This effect appeared to be mediated by a heightened sensitivity to the A[T.sub.1] receptor among betamethasone-exposed sheep. Sodium excretion initially decreased in both groups during ANG II infusion; however, a rebound was observed after 24 h. A[T.sub.1] blockade was followed by a significant rebound after 24 h in both groups. A[T.sub.2] blockade blunted the 24-h rebound effect among the vehicle-exposed sheep compared with the betamethasone-exposed sheep. In conclusion, antenatal corticosteroid exposure appears to modify renal responsiveness to ANG II by increasing A[T.sub.1]- and decreasing A[T.sub.2] receptor-mediated actions particularly as related to renal blood flow and sodium excretion. angiotensin receptor; renal plasma flow; glomerular filtration rate; corticosteroids doi: 10.1152/ajprenal.00497.2009.

Woods LL, Morgan TK, Resko JA. Castration fails to prevent prenatally programmed hypertension in male rats. Am J Physiol Regul Integr Comp Physiol 298: Rl111-Rl116, 2010. First published January 27, 2010; doi:10.1152/ajpregu.00803.2009.--Male offspring of rats that were modestly protein restricted during pregnancy become hypertensive as adults, whereas their female littermates remain normotensive. The purpose of this study was to determine the role of testosterone in promoting this sexual dimorphism of prenatally programmed hypertension. Rats were fed either a normal (19% protein, NP) or modestly protein-restricted (8.5% protein, LP) diet throughout pregnancy. Male offspring either remained intact or were castrated (CAS) at 30 days of age. Female offspring remained intact. At ~22 wk of age, the offspring were chronically instrumented for measurement of mean arterial pressure and renal function. Intact male LP offspring were hypertensive compared with male NP offspring (138 [+ or -] 2 vs. 130 [+ or -] 2 mmhg, P < 0.007), whereas female LP offspring were normotensive (123 [+ or -] 1 vs. 122 [+ or -] 2 mmHg in NP females). In CAS males, blood pressure in both diet groups was not different from that in intact males of the same group (138 [+ or -] 3 mmHg in LP CAS males, and 131 [+ or -] 2 mmHg in NP CAS males). Glomerular filtration rate and effective renal plasma flow were also not significantly affected by castration. However, castration significantly reduced protein excretion in LP males to levels not different from those in NP CAS and intact males. Renal histopathology scores showed a similar pattern. Thus removal of androgens by castration failed to provide any protective effect against the hypertension programmed by maternal protein restriction. Castration also failed to abolish the sex difference in blood pressure in both diet groups. These findings suggest that the lifelong presence of normal levels of testicular hormones does not play a major role either in maintaining baseline blood pressure higher in males than in females, or in promoting further elevations in blood pressure in males due to prenatal undernutrition. However, androgens such as testosterone may promote renal injury in LP males. dietary protein restriction; sexual dimorphism; glomerular filtration rate doi: 10.1152/ajpregu.00803.2009.

Superoxide ([O.sub.2.sup.-]) enhances tubuloglomerular feedback (TGF) by scavenging nitric oxide at the macula densa (MD). The primary source of [O.sub.2.sup.-] in the MD during TGF is NADPH oxidase, which is activated by membrane depolarization. While Rac, a small GTP-binding protein, has been shown to enhance NADPH oxidase activity, its role in [O.sub.2.sup.-] generation by the MD is unknown. We hypothesized that depolarization of the MD leads to translocation of Rac to the apical membrane, and its activation, in turn, augments [O.sub.2.sup.-] generation during TGF. We tested this by measuring membrane potential and increased [O.sub.2.sup.-] levels during TGF responses in isolated, perfused tubules containing the intact MD plaque. Switching tubular NaCl from 10 to 80 mM, which induces TGF, depolarized membrane potential by 28.4 [+ or -] 4.5% from control (P < 0.05) and [O.sub.2.sup.-] levels from 124 [+ or -] 19 to 361 [+ or -] 27 U/min. This NaCl-induced depolarization and 02 generation were blocked by a [Cl.sup.-] channel blocker, 5-nitro-2(3-phenylpropylamino) benzoic acid (NPPB; [10.sup.-6] M). Inhibition of Rac blunted NaCl-induced [O.sub.2.sup.-] generation by 47%. When the NaCl content of the MD perfusate was increased from 10 to 80 mM, immunointensity of Rac on the apical side increased from 32 [+ or -] 3.1 to 46 [+ or -] 2.5% of the total immunofluorescence in the MD, indicating that high NaCl induces the translocation of Rac to the apical membrane. This NaCl-induced Rac translocation was blocked by a [Cl.sup.-] channel blocker, NPPB, indicating that depolarization of the MD induced Rac translocation. In conclusion, we found that depolarization of the MD during TGF leads to translocation of Rac to the apical membrane, which enhances [O.sub.2.sup.-] generation by the MD. glomerular filtration rate; NADPH oxidase; NaCl; translocation doi: 10.1152/ajpregu.00622.2009

The transfer of albumin from blood to tissue has been found to be increased in caveolin-1 knockout (KO) mice. This has been considered to refect increased microvascular permeability, conceivably caused by an increased endothelial production of nitric oxide (NO) in these mice. To investigate whether such an increase in NO production would also affect glomerular barrier characteristics, the glomerular sieving coefficients ([theta]) to neutral FITC-Ficoll 70/400 (molecular radius 13-90 [Angstrom]) were determined in caveolin-1 KO mice vs. their wild-type counterparts. The [theta] for Ficoll were assessed using high-performance size-exclusion chromatography on blood and urine samples. Furthermore, the transcapillary escape rate (TER) of [sup.125]I-labeled albumin and plasma volume (PV) were determined in both types of mice. The kidney expressed low levels of caveolin- 1 compared with the lung and bladder, but immunofluorescence associated with vascular structures was evident. Staining was lost in the caveolin-1 KO kidney, as was caveolin-1 expression in the lung and bladder. Despite an increase in the glomerular filtration rate in caveolin-1 KO mice (0.23 [+ or -] 0.04 vs. 0.10 [+ or -] 0.02 ml/min; both n = 7; P < 0.05), the glomerular Ficoll sieving curves were nearly identical. Furthermore, caveolin-1 KO mice showed an increased PV (6.59 [+ or -] 0.42 vs. 5.18 [+ or -] 0.13 ml/100 g; P < 0.01) but only a tendency toward an increased TER (14.69 [+ or -] 1.59 vs. 11.62 [+ or -] 1.62%/h; not significant). It is concluded that in caveolin-1 KO mice the glomerular permeability was not increased, despite the presence of glomerular hyperfiltration. The present data are in line with the concept that the increased transvascular albumin leakage previously found in mice lacking caveolin-1 may be due to an elevation in systemic microvascular pressure due to precapillary vasodilatation, rather than being a consequence of increased microvascular permeability per se. capillary permeability; transcytosis; nitric oxide; transcapillary escape rate; glomerular filtration; macromolecules

Peroxynitrite ([ONOO.sup.-]) is formed endogenously by the reaction of nitric oxide (NO) and superoxide ([O.sub.2.sup.-]). To examine the hypothesis that [OONO.sup.-] cause renal vasodilation at low concentrations but cause vasoconstriction at higher concentrations, we examined renal responses to intraarterial infusion of incremental doses of [OONO.sup.-] (10, 20, and 40 [micro]g x [kg.sup.-1] x [min.sup.-1]; 45 min each) in anesthetized rats. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by PAH and inulin clearance. In control rats (n = 6), low dose (10 [micro]g x [kg.sup.-1] x [min.sup.-1]) of [OONO.sup.-] increased RBF by 10 [+ or -] 3% and GFR by 15 [+ or -] 5%. The higher doses (20 and 40 [micro]g x [kg.sup.-1] x [min.sup.-1]) mostly reversed these responses which were -7 [+ or -] 4 and -27 [+ or -] 7% (P < 0.05) in RBF and -0.1 [+ or -] 4.8 and -14 [+ or -] 12% in GFR, respectively. There were no appreciable changes in urine flow (V) and sodium excretion ([U.sub.Na]V) during [OONO.sup.-] infusion. However, in rats pretreated with NO synthase (NOS) inhibitor, L-NAME (50 [micro]g x [kg.sup.-1] x [min.sup.-1]; n = 5), these doses of [OONO.sup.-] significantly reduced RBF (-26 [+ or -] 7, -27 [+ or -] 6, and -44 [+ or -] 3%) and GFR (-21 [+ or -] 6, -25 [+ or -] 8, and -32 [+ or -] 12%) with variable increases in V or [U.sub.Na]V. Long-term infusion of [OONO.sup.-] (10 [micro]g x [kg.sup.-1] x [min.sup.-1] for 75 min) in another set of control rats (n = 5) also showed similar vasodilator and hyperfiltration responses. These data indicate that [OONO.sup.-] acts as an oxidant at high concentration but provides renoprotective function at low concentration that depends on intact NOS activity. nitric oxide; superoxide; oxidative stress; renal blood flow; glomerular filtration rate

SGK1 is critically important for mineralocorticoid/salt-induced glomerular injury. SGK1 inactivates GSK3, which downregulates Snail, a DNA-binding molecule repressing the transcription of nephrin, a protein critically important for the integrity of the glomerular slit membrane. PKB/SGK-dependent GSK regulation is disrupted in mice carrying a mutation, in which the serine in the SGK/PKB-phosphorylation consensus sequence is replaced by alanine. The present study explored whether PKB/SGK-dependent GSK3 regulation influences glomerular proteinuria. Gene-targeted knockin mice with mutated and thus PKB/SGK-resistant GSK3[alpha],[beta] ([gsk3.sup.KI]) were compared with their wild-type littermates ([gsk3.sup.WT). [gsk3.sup.KI] and [gsk3.sup.WT] mice were implanted with DOCA release pellets and offered 1% saline as drinking water for 21 days. Under standard diet, tap water intake and absence of DOCA, urinary flow rate, glomerular filtration rate, and urinary albumin excretion were significantly larger and blood pressure was significantly higher in [gsk3.sup.KI] than in [gsk3.sup.WT] mice. Within 18 days, DOCA/salt treatment significantly increased fluid intake and urinary flow rate, urinary protein and albumin excretion, and blood pressure in both genotypes but the respective values were significantly higher in [gsk3.sup.KI] than in [gsk3.sup.WT] mice. Plasma albumin concentration was significantly lower in [gsk3.sup.KI] than in [gsk3.sup.WT] mice. Proteinuria was abrogated by lowering of blood pressure with [[alpha].sub.1]-blocker prazosin (1 [micro]g/g body wt) in 8-mo-old mice. According to immunofluorescence, nephrin at 3 and 8 mo and podocin expression at 3 mo were significantly lower in [gsk3.sup.KI] than in [gsk3.sup.WT] mice. After 18 days, DOCA/salt treatment renal glomerular sclerosis and tubulointerstitial damage were significantly more pronounced in [gsk3.sup.KI] than in [gsk3.sup.WT] mice. The observations reveal that disruption of PKB/SGK-dependent regulation of GSK3 leads to glomerular injury with proteinuria, which may at least partially be secondary to enhanced blood pressure. glomerular filtration rate; water; DOCA; albumin; nephrin

Ischemic nephropathy describes progressive renal failure, defined by significantly reduced glomerular filtration rate, and may be due to renal artery stenosis (RAS), a narrowing of the renal artery. It is unclear whether ischemia is present during RAS since a decrease in renal blood flow (RBF), [O.sub.2] delivery, and [O.sub.2] consumption occurs. The present study tests the hypothesis that despite proportional changes in whole kidney [O.sub.2] delivery and consumption, acute progressive RAS leads to decreases in regional renal tissue [O.sub.2]. Unilateral acute RAS was induced in eight pigs with an extravascular cuff. RBF was measured with an ultrasound flow probe. Cortical and medullary tissue oxygen [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] of the stenotic kidney was measured continuously with sensors during baseline, three sequentially graded decreases in RBF, and recovery. [O.sub.2] consumption decreased proportionally to [O.sub.2] delivery during the graded stenosis (19 [+ or -] 10.8, 48.2 [+ or -] 9.1, 58.9 [+ or -] 4.7 vs. 15.1 [+ or -] 5, 35.4 [+ or -] 3.5, 57 [+ or -] 2.3%, respectively) while arterial venous [O.sub.2] differences were unchanged. Acute RAS produced a sharp reduction in [O.sub.2] efficiency for sodium reabsorption (P < 0.01). Cortical [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] decreases are exceeded by medullary decreases during stenosis (34.8 [+ or -] 1.3%). Decreases in tissue oxygenation, more pronounced in the medulla than the cortex, occur despite proportional reductions in [O.sub.2] delivery and consumption. This demonstrates for the first time that hypoxia is present in the early stages of RAS and suggests a role for hypoxia in the pathophysiology of this disease. Furthermore, the notion that arteriovenous shunting and increased stoichiometric energy requirements are potential contributors toward ensuing hypoxia with graded and progressive acute RAS cannot be excluded. ischemia; renal tissue oxygenation; renal blood flow; pig

Rat glomerular mesangial cells (MC) become lipid-laden foam cells when they are exposed to IGF-1. IGF-1 increased accumulation of triglyceride (TG) 2.5-fold in MC after 7 days. TG accumulation resulted from enhanced macropinocytosis and decreased efflux secondary to a 40-50% reduction in peroxisome proliferator-activated receptor (PPAR)-[delta] (PPAR[delta]). There was no evidence of primary or secondary changes in cholesterol or TG synthesis, increased uptake by LDL or scavenger receptors, or reduced efflux via ATP-binding cassette A-1. Although the lipid moiety taken up can be influenced by the concentration of cholesterol or TG in the medium, in standard medium MC preferentially accumulate TG. TG-rich MC foam cells tail to contract in response to angiotensin II (Berfield AK, Andress DL, and Abrass CK. Kidney Int 62: 1229-1237, 2002); however, their migratory response to IGF binding protein-5 is unaffected. This differs from cholesterol loading, which impairs both phagocytosis and migration. These findings have important implications for understanding the mechanisms that contribute to lipid accumulation in MC and the functional consequences of different forms of foam cells. These observations are relevant to understanding vascular disease and progressive renal diseases that are accelerated by abnormalities in lipid metabolism. chronic kidney disease; cholesterol; peroxisome proliferator-activated receptor; foam cells

We evaluated the glomerular filtration rate (GFR) in 34 subjects with membranous nephropathy (MN) of new onset. We used physiological techniques to measure GFR, renal plasma flow, and oncotic pressure and computed a value for the two-kidney ultrafiltration coefficient ([K.sub.f]). A morphometric analysis of glomeruli in the diagnostic biopsy permitted computation of the single-nephron ultrafiltration coefficient (SN[K.sub.f]). MN subjects were divided into two groups: moderate or severe, according to whether GFR was depressed by less or more than 50%. SN[K.sub.f] was subnormal but similar in moderate and severe MN. In contrast, two-kidney [K.sub.f] was significantly more depressed in severe than in moderate MN. We estimated the total number of functioning glomeruli ([N.sub.g]) by dividing two-kidney [K.sub.f] by SN[K.sub.f]. Whereas mean Ng was similar in controls and moderate MN (1.5 and 1.4-1.7 x [10.sup.6], respectively), it was significantly lower in severe MN (0.5 x 106). This degree of glomerulopenia was not reflected in the rate of global sclerosis. We conclude that a combination of depressed SN[K.sub.f] (due to foot process broadening) and profound glomerulopenia accounts for GFR depression of >50% early in the course of MN. The cause of the glomerulopenia remains to be elucidated. glomerular filtration rate; glomerular hemodynamics; ultrafiltration coefficient; glomerular morphometry; glomerular number