Severity Of Acute Renal Failure Research Articles

Épidémiologie de l’insuffisance rénale aiguë au cours de la dengue dans la ville de Ouagadougou

AimDescribe acute renal failure during dengue fever in Ouagadougou, in a context of almost nonexistent african data on the subject. Patients and methodThe study was cross-sectional and descriptive with a retrospective collection of data in 13 health structures. It concerned a period of 16 months. Included were suspected cases of dengue fever following the guidelines of the ministry of health and for whom an ARF was diagnosed. The acute renal failure and its severity were defined according to KDIGO's recommendations. ResultSixty-seven cases (sex ratio 2.7 ; mean age 39.6±16.7 years) of acute renal failure were noted among 316 dengue fever patients, or 21.2%. The mean of serum creatinine on admission was 440.7±504.2 μmol/L. The acute renal failure severity was classified at stage 3 in 29 cases, or 43.3%. The most common etiopathogenic factors were those responsible for renal hypoperfusion in 47 cases, or 70.2%; 14 cases of brown macroscopic hematuria, or 20.9%, were observed. Nine patients, or 13.4%, were taken in conventional acute hemodialysis. Six cases of death, a lethality rate of 9%, were observed. ConclusionThe acute renal failure in our dengue fever patients population was very common, severe, and highly lethal. The prognosis should improve with early management. It would be even better to promote primary prevention through effective vector control.

SiRNA-silencing of CD40 attenuates unilateral ureteral obstruction-induced kidney injury in mice.

BackgroundThe costimulatory CD40-CD40L pathway plays a role in kidney inflammation. We have previously reported that renal CD40 upregulation precedes cellular interstitial infiltrate and fibrosis in the unilateral ureteral obstruction (UUO) model. Here we sought to evaluate whether the administration of siRNA-CD40 has a therapeutic effect in a reversible unilateral ureteral obstruction (D-UUO) mice model.MethodsEight week-old C57BL6J male mice were divided into four groups: Vehicle (Phosphate-buffered saline) (n = 8); siRNA SC (non-specific siRNA) (n = 6); siRNA-CD40 (n = 8) and WT (wild type) (n = 6) mice. UUO was performed with a microvascular clamp. At day 3 after surgery, the ureteral clamp was removed and nephrectomy of the contralateral kidney was performed. Immediately, PBS, siRNA SC (50μg) or siRNA-CD40 (50μg) was administrated via the tail vein. Mice were killed 48h hours after the siRNA or saline administration. Wild type (WT) mice were used as controls. Blood samples were collected for measuring creatinine and blood urea nitrogen (BUN). Histology and kidney mRNA expression were performed.ResultsThe administration of siRNA-CD40 reduced significantly the severity of acute renal failure associated with UUO. Pathologic analysis showed reduction of tubular dilation, interstitial fibrosis, F4/80 macrophage and CD3 (T cell) infiltration in animals treated with siRNA-CD40. Furthermore, kidney mRNA gene expression analysis showed significantly lower levels of macrophage markers (F4/80 and Mannose receptor), fibrosis matrix proteins (Fibronectin, MMP-9, Collagen IV and α-SMA), pro-inflammatory cytokines (iNOS and MCP-1) and the pro-fibrotic molecule TGF-β1 in siRNA-CD40.ConclusionsThe administration of siRNA-CD40 therapy reduces the severity of the acute kidney injury induced by obstructive uropathy and promotes kidney repair. This strategy seems suitable to be tested in humans.

A study on incidence and severity of acute renal failure and its association with parasite density in hospitalised patients with falciparum malaria

Aims of the study: To find out the incidence of acute renal failure in falciparum malaria and to correlate between the degree of parasitism at presentation with acute renal failure and its outcome in falciparum malaria. Methodology: Each patient with a history of fever, suggestive of severe malaria was subjected to peripheral blood smear examinations, up to 3 samples were examined or till positive and/or Pf antigen positive cases. The selected patients were then grouped according to the clinical features, laboratory parameters and were followed up for the outcome. Results: Out of the 50 cases of acute renal failure due to falciparum malaria, 21 had Parasite density <5% (42%), 13 had 5-10%(26%) and 16 had >10%(32%). Out of 21 cases of mild ARF 12 patients had parasite density<5% and 9 had >5%. Out of 29 cases of severe ARF 9 patients had parasite density<5% and 20 had >5%. Dialysis was done in a total of 31 cases (62%). In the severe form of acute renal failure. hemodialysis was required in 29 cases (58%), in the milder form of renal failure; only 2 cases (4%) required hemodialysis. Rests of the cases were managed by conservative treatment. Conclusion: Parasite Density has significant impact to predict the severity of renal failure, duration of hospital stays as well as the number of dialysis required. As the study was conducted with small number of cases, further study is necessary with large number of cases to arrive at a conclusion regarding the malady of acute renal failure in falciparum malaria.

Investigation of a Rise in Obstetric Acute Renal Failure in the United States, 1999-2011.

To estimate whether the reported increase in obstetric acute renal failure in the United States was attributable to a concurrent rise in postpartum hemorrhage, a change in other risk factors, or changes in the diagnosis of acute renal failure. We conducted a retrospective cohort study to quantify temporal trends in acute renal failure among 10,969,263 hospital deliveries in the United States from 1999 to 2011 using data from the Nationwide Inpatient Sample. Dialysis and maternal death were used as markers of severe acute renal failure. Logistic regression was used to determine whether changes in risk factors explained the temporal rise in acute renal failure. Obstetric acute renal failure rose from 2.4 to 6.3 per 10,000 deliveries between 1999-2001 and 2010-2011, a 10% yearly increase (95% confidence interval [CI] 8-11%) and adjustment for risk factors only partially explained the rise (adjusted yearly increase 6%, 95% CI 5-8%). The overall severity of acute renal failure decreased, although acute renal failure with dialysis rose from 0.27 to 0.36 per 10,000 deliveries (P for trend=.01), and acute renal failure associated with maternal death increased from 0.13 to 0.23 per 10,000 deliveries (P for trend=.01). The temporal increase in acute renal failure with dialysis was abolished by adjustment for chronic kidney disease and chronic hypertension. Changes in diagnosis or ascertainment have led to substantial increases in obstetric acute renal failure, whereas increases in chronic kidney disease and chronic hypertension among pregnant women have resulted in modest but significant increases in acute renal failure with dialysis.

Drug-related acute renal failure in hospitalised patients

IntroductionThe information available on the incidence and the characteristics of patients with acute renal failure (ARF) related to drugs is scarce. ObjectivesTo estimate the incidence of drug-related ARF in hospitalised patients and to compare their characteristics with those of patients with ARF due to other causes. Material and methodsWe selected a prospective cohort of patients with ARF during hospital admission (July 2010–July 2011). Information on patients’ demographics, medical antecedents, ARF risk factors, ARF severity according to the RIFLE classification and hospital drug administration was collected. We analysed the relationship of drugs with the ARF episodes using Spanish Pharmacovigilance System methods and algorithm. ResultsA total of 194 cases had an episode of hospital-acquired ARF. The median age of patients was 72 years [IQR 20]; 60% were men. The ARF incidence during hospitalisation was 9.6 per 1000 admissions. According to the RIFLE classification, a risk of kidney damage or kidney injury was present in 77.8% of cases. In 105 (54.1%) cases, ARF was drug-related; the drugs most frequently involved were diuretics, agents acting on the renin–angiotensin system, immunosuppressants, β-blocking agents, calcium channel blockers, contrast media and non-steroid anti-inflammatory drugs. Patients with drug-related ARF had more multi-morbidity, fewer ARF risk factors and lower mortality. ConclusionsHalf of ARF episodes during hospitalisation were drug related. Patients with drug-related ARF had higher cardiovascular morbidity than those with ARF related to other causes, but they had a lower frequency of ARF risk factors and mortality.

Insuficiencia renal aguda relacionada con medicamentos en pacientes hospitalizados

IntroductionThe information available on the incidence and the characteristics of patients with acute renal failure (ARF) related to drugs is scarce. ObjectivesTo estimate the incidence of drug-related ARF in hospitalised patients and to compare their characteristics with those of patients with ARF due to other causes. Material and methodsWe selected a prospective cohort of patients with ARF during hospital admission (July 2010-July 2011). Information on patients’ demographics, medical antecedents, ARF risk factors, ARF severity according to the RIFLE classification and hospital drug administration was collected. We analysed the relationship of drugs with the ARF episodes using Spanish Pharmacovigilance System methods and algorithm. ResultsA total of 194 cases had an episode of hospital-acquired ARF. The median age of patients was 72 years [IQR 20]; 60% were men. The ARF incidence during hospitalization was 9.6 per 1,000 admissions. According to the RIFLE classification, a risk of kidney damage or kidney injury was present in 77.8% of cases. In 105 (54.1%) cases, ARF was drug-related; the drugs most frequently involved were diuretics, agents acting on the renin-angiotensin system, immunosuppressants, β-blocking agents, calcium channel blockers, contrast media and non-steroid anti-inflammatory drugs. Patients with drug-related ARF had more multi-morbidity, fewer ARF risk factors and lower mortality. ConclusionsHalf of ARF episodes during hospitalisation were drug related. Patients with drug-related ARF had higher cardiovascular morbidity than those with ARF related to other causes, but they had a lower frequency of ARF risk factors and mortality.

OCCURRENCE AND SEVERITY OF ACUTE RENAL FAILURE IN MALARIA

Objective: To assess the occurrence and severity of acute renal failure in hospitalized malaria patients. Patients and Methods: In a hospital based set up out of 400 cases of fever, 102 were detected with positive malarial parasite. Clinical history and assessment were recorded in all the study patients and all other known etiological causes of fever and jaundice were excluded by relevant investigations. The renal function test including both Blood urea and serum creatinine was done for the patients. Acute Renal Failure(ARF): Those with serum creatinine >1.5 mg% and normal size kidneys on USG were included in ARF and further divided in 3 groups: mild (Scr < 2 mg%), moderate (Scr 2-5 mg%) and severe (Scr>5mg%). Result: Of total 102 malaria positive patients, Plasmodium falciparum was seen in 6 patients (5.88%), plasmodium vivax in 46(45.09%) and mixed infection in 50patients (49.01%). Eleven patients (10.78%) out of 102 patients had ARF and malarial positive. Plasmodium falciparum was the causative agent in 1; P.vivax in 3 and mixed infection in 7 patients. Out of 102 patients two patients had severe renal failure with creatinine values more than 5mg/dl. 89.22% of patients with malaria had serum creatinine below 1.5mg/dl. Conclusion: It can be concluded that in south Kanara region it is the mixed and plain P.vivaxwhich was more common. ARF occurs commonly in plasmodium falciparum malaria but in our study it has been reported in mixed & plasmodium vivax.

Partial protection of verapamil against gentamicin nephrotoxicity in rats

A number of male rats (40) were used to test the protective efficacy of verapamil a calcium channel blocker (CCB) against gentamicin nephrotoxicity.They were divided into four groups: group-1 control, giving only water, group- 2, they were administered gentamicin IP 80 mg/Kg, group-3, administeredverapamil orally 10 mg/Kg and group-4 administered gentamicin and verapamil at the same time. The period of study was 10 days.Nephrotoxicity was induced by using gentamicin for 7 days; this was evidenced by marked elevation in blood urea nitrogen (BUN) andplasma creatinine (Pcr) when compared with control. BUN increased from 20±1.4 to 205±7 and Pcr from 0.75±0.08 to 4.2±0.3 mg/100 ml). Coadministration of verapamil with gentamicin decreased the rise in BUN and Pcr, their values reached to 90±13 and 1.5±0.9 mg/100 ml respectively.Our data suggest that supplementation of verapamil decreased the severity of acute renal failure (ARF) in rats, this supports previous studies in which CCBs offer renoprotection in ARF, the exact mechanism of this protection need further study.

Parenteral iron formulations differentially affect MCP-1, HO-1, and NGAL gene expression and renal responses to injury

Despite their prooxidant effects, ferric iron compounds are routinely administered to patients with renal disease to correct Fe deficiency. This study assessed relative degrees to which three clinically employed Fe formulations [Fe sucrose (FeS); Fe gluconate (FeG); ferumoxytol (FMX)] impact renal redox- sensitive signaling, cytotoxicity, and responses to superimposed stress [endotoxin; glycerol-induced acute renal failure (ARF)]. Cultured human proximal tubule (HK-2) cells, isolated proximal tubule segments (PTS), or mice were exposed to variable, but equal, amounts of FeS, FeG, or FMX. Oxidant-stimulated signaling was assessed by heme oxygenase-1 (HO-1) or monocyte chemoattractant protein (MCP)-1 mRNA induction. Cell injury was gauged by MTT assay (HK-2 cells), %LDH release (PTS), or renal cortical neutrophil gelatinase-associated lipoprotein (NGAL) protein/mRNA levels. Endotoxin sensitivity and ARF severity were assessed by TNF-alpha and blood urea nitrogen concentrations, respectively. FeS and FeG induced lethal cell injury (in HK-2 cells, PTS), increased HO-1 and MCP-1 mRNAs (HK-2 cells; in vivo), and markedly raised plasma ( approximately 10 times), and renal cortical ( approximately 3 times) NGAL protein levels. Both renal and extrarenal (e.g., hepatic) NGAL production likely contributed to these results, based on assessments of tissue and HK-2 cell NGAL mRNA. FeS pretreatment exacerbated endotoxemia. However, it conferred marked protection against the glycerol model of ARF (halving azotemia). FMX appeared to be "bioneutral," as it exerted none of the above noted FeS/FeG effects. We conclude that 1) parenteral iron formulations that stimulate redox signaling can evoke cyto/nephrotoxicity; 2) secondary adaptive responses to this injury (e.g., HO-1/NGAL induction) can initiate a renal tubular cytoresistant state; this suggests a potential new clinical application for intravenous Fe therapy; and 3) FMX is bioneutral regarding these responses. The clinical implication(s) of the latter, vis a vis the treatment of Fe deficiency in renal disease patients, remains to be defined.

Acute Renal Failure in the Neonate

Although the exact prevalence of acute renal failure (ARF) in the neonate is difficult to determine precisely, patients who have mild-to-severe ARF are common in most neonatal intensive care units (NICUs). In most instances, the cause of failure is prerenal, in which cardiac output or renal blood flow are diminished, but intrinsic renal injury or postrenal obstructive processes also occur. By considering normal renal physiology, the mechanisms through which renal failure develops can be understood. This understanding is important in limiting the extent of injury and in developing therapies to control the effects of renal dysfunction on fluid and electrolyte balance, acidosis, and nutrition. Outcome and prognosis depend on comorbidities and the presence of failure in other organs as well as the cause and severity of ARF. Permanent effects may not be apparent until later in childhood, mandating careful follow-up and monitoring.

Does concurrent renin‐angiotensin‐aldosterone blockade in (older) chronic kidney disease patients play a role in the acute renal failure epidemic in US hospitalized patients?—Three cases of severe acute renal failure encountered in a northwestern Wisconsin Nephrology practice

Following the publication of several large multicenter randomized placebo-controlled trials showing reno-protection with renin-angiotensin-aldosterone (RAAS) blockade, the last 2 decades have witnessed an escalating use of the angiotensin-converting enzyme inhibitors and the angiotensin receptor blockers. Simultaneously, we continue to experience an increasing epidemic of acute renal failure (ARF) both in community-based and in hospital-based studies. Even though other factors would be contributing to this ARF epidemic, recent published data have raised concerns of a plausible connection between increased use of the RAAS blocking agents and this ARF epidemic. In our 4-nephrologist northwestern practice, we have, in recent years, anecdotally encountered an increasing number and severity of ARF, often with hyperkalemia, sometimes requiring dialysis intervention, in patients concurrently on these agents. Over the 3-day Christmas weekend in 2007, we treated 3 cases of severe ARF (peak serum creatinine of 7.0 (3.3-9.2) mg/dL), all on RAAS blockade. Renin-angiotensin-aldosterone blockade was promptly discontinued. All patients received intravenous fluid repletion. Kidney function rapidly normalized in 2 within 1 week. One patient required hemodialysis for 14 days before his serum creatinine returned to normal after 5 weeks. All 3 patients have continued to maintain baseline serum creatinine several months later, still off RAAS blockade. The mean baseline eGFR for the 3 patients was 46 (41-51) mL/min/1.73 m(2) body surface area. This phenomenon of ARF exacerbation, which may have implications for chronic kidney disease progression to ESRD especially in the elderly, merits further study. We support the recommendation that (older, >65 years old) chronic kidney disease patients on RAAS blocking agents should have the medications temporarily suspended during any acute illness, before major surgical procedures, and before iodinated contrast or oral phosphate sodium administration.

Challenges of Genomics and Proteomics in Nephrology

An increasing number of patients suffering from renal diseases and limitations in standard diagnostic and therapeutic approaches has created an intense interest in applying genomics and proteomics in the field of nephrology. Genomics has provided a vast amount of information, linking the gene activity with disease. However, proteomic technologies allow us to understand proteins and their modifications, elucidating properties of cellular behavior that may not be reflected in analysis of gene expression. The application of these innovative approaches has recently yielded the promising new urinary biomarkers for acute kidney injury and chronic kidney disease, thus providing a better insight in renal pathophysiology and establishing the basis for new therapeutic strategies. Despite significant improvements in therapeutics, the mortality and morbidity associated with acute renal failure (ARF) remain high. The lack of early markers for ARF causes an unacceptable delay in initiating therapy. These biomarker panels will probably be useful for assessing the duration and severity of ARF, and for predicting progression and adverse clinical outcomes. Kidney failure leads to the uremic syndrome characterized by accumulation of uremic toxins, which are normally cleared by the kidneys. Proteomics has gained considerable interest in this field, as a new and promising analytical approach to identify new uremic toxins. The urinary proteome as a tool for biomarker discovery is still in its early phase. A major challenge will be the integration of proteomics with genomics data and their functional interpretation in conjunction with clinical results and epidemiology.

Role of Age‐Dependent Changes in MMP Expression in Acute Kidney Injury

Aging is associated with an increased incidence and severity of acute renal failure. However, the molecular mechanism(s) underlying the increased susceptibility to injury remain undefined. Given the emerging role of MMPs in ischemic renal injury, the renal mRNA expression of MMPs and their endogenous inhibitors, TIMPs (tissue inhibitor of metalloproteinases), were also examined in young, aged‐AL and aged‐CR rats. Interestingly, age‐dependent increases in the expression of MMP‐7, ‐9, ‐13, and ‐14 were seen, and these changes were attenuated by caloric restriction. The expression of TIMP‐1, but not TIMP‐2 or ‐3, was increased by age and attenuated by caloric restriction. Changes in MMP expression gene expression were paralleled by an age‐dependent increase in collagenase, gelatinase, and membrane type‐MMP activity. Specific increases in MMP‐7, ‐9, and ‐13 activity was seen in urine and kidney tissue, respectively. These results suggest an association between the age‐related increase in susceptibility to injury and overexpression of select MMPs (‐7, ‐9, ‐13, and ‐14) in the kidney, implying a therapeutic potential for inhibition of these MMPs in acute kidney injury.

Glomerulonephritis causing acute renal failure during the course of bacterial infections. Histological varieties, potential pathogenetic pathways and treatment

To illustrate diagnostic approaches, potential pathogenetic differences, epidemiological implications and therapeutic dilemmas posed by glomerulonephritis (GN) with acute renal failure (ARF) complicating bacterial infections, we analyzed the course of four male patients, aged 53-71 years, who developed GN and ARF following bacterial infections. The first two patients developed GN with immunoglobulin A (IgA) deposits after infections with hospital-acquired methicillin resistant Staphylococcus aureus (MRSA). Clinical, serologic and histological features, classification of GN and treatment differed between the two patients. In the first patient, serological features (transient hypocomplementemia, normal serum protein electrophoresis) and histological findings were consistent with typical post-infectious GN. Treatment with antibiotics alone resulted in normalization of the renal function despite the severity of ARF, which required temporary hemodialysis. In the second patient, serological features (normal serum complement, polyclonal elevation of gamma globulins) and histological picture of the kidneys were characteristic of IgA nephropathy with fibrocellular crescents, and skin histology was consistent with vasculitis. Cyclophosphamide and corticosteroids were added to the antibiotics, with partial improvement of the renal failure. The third patient developed simultaneous acute rheumatic fever and post-streptococcal GN causing severe ARF requiring hemodialysis. Complete recovery of ARF and migratory polyarthritis followed initiation of corticosteroids. The fourth patient developed ARF and cerebral vasculitis following a prolonged course of Streptococcus mutans endocarditis with delayed diagnosis. He also developed multiple serological abnormalities including elevated titers of antineutrophil cytoplasmic antibodies (ANCA), antinuclear antibodies (ANA), anti-phospholipid antibodies, rheumatoid factor, and modest hypocomplementemia. Kidney biopsy revealed ANCA-mediated focal GN with 10% crescents and acute interstitial nephritis. Treatment with cyclophosphamide plus corticosteroids, but not with antibiotics alone, resulted in resolution of both the ARF and the features of cerebral vasculitis. GN following bacterial infections may have various pathogenetic mechanisms, presents complex diagnostic challenges, may be preventable in the case of hospital-acquired MRSA, and, in addition to antibiotics, may require immunosuppressive therapy in carefully selected and monitored cases.

Increased Susceptibility of Aging Kidney to Ischemic Injury: Role of Aberrant MMP‐7 Expression

Aging is associated with an increased incidence and severity of acute renal failure; however, the molecular mechanisms underlying the increased susceptibility remain undefined. These experiments were designed to investigate the influence of age on the response of the kidney to ischemia. Renal slices were prepared from young (5 month), aged ad libitum (24 month) and aged caloric restricted (24 month) male Fischer 344 rats and subjected to ischemic stress (anoxia, 100% N2) for 0–60 min or to the nephrotoxicant cisplatin (2 mM, 4 hr). As assessed by intracellular ATP and GSH content, and LDH and alpha-GST leakage into the culture media, slices from aged ad libitum rats were more susceptible to injury than young counterparts. Importantly, caloric restriction attenuated this increased susceptibility to injury. In an attempt to identify molecular pathway(s) underlying this response, microarray analysis was performed on tissue harvested from the same animals used for the functional analysis. RNA was isolated and the corresponding cDNA was hybridized to CodeLink™ Rat Whole Genome Bioarray slides. Subsequent gene expression analysis was performed using GeneSpring software. Using a 2-fold difference as a cut-off and a Welch ANOVA (Benjamini and Hochberg False Discovery Rate of 0.05), we identified 131 genes whose pattern of expression suggested that caloric restriction attenuated a change induced by aging. The expression of 42 genes was reduced during aging but rescued by caloric restriction. The expression of 89 genes was increased during aging but attenuated by caloric restriction, including MMP-7. In summary, we have identified several changes in gene expression that may be associated with the increased susceptibility of aging kidney to ischemic insult.

Acute renal failure independently predicts mortality after myeloablative allogeneic hematopoietic cell transplant

Patients undergoing myeloablative allogeneic hematopoietic cell transplantation (HCT) have a high incidence of acute renal failure (ARF). However, it is unclear if ARF is independently associated with mortality after this procedure. We performed meta-analysis of published reports on ARF after myeloablative allogeneic HCT. Four databases (MEDLINE, Cochrane Library, PubMed, Web of Science) and hand searching of conference proceedings were used to identify the studies. ARF was defined as the doubling of serum creatinine occurring within the first 100 days after HCT. The absolute and the relative risks for death after ARF were calculated for every study. The combined relative risk was calculated using the random effects model. Also, multivariate analysis of patient level data was performed on patients from The University of Colorado to establish independent association between ARF and mortality. One thousand two hundred and eleven patients were included in the meta-analysis from the 6 published reports in the literature. The overall incidence of ARF varied from 42% to 84% in these studies. On combining the studies by random-effects model, the relative risk of death after ARF was 2.22 (95%CI 1.38-3.5, P < 0.001). The analysis of patient level data from the University of Colorado demonstrated increasing mortality with worsening grades of ARF. After controlling for various demographic and clinical variables with logistic regression, patients who required dialysis had a 6.8-fold higher association with mortality. ARF appears to independently influence mortality after myeloablative allogeneic HCT. Future studies should be aimed at interventions that can reduce the incidence and severity of ARF with this procedure.

Comparison of ARF after myeloablative and nonmyeloablative hematopoietic cell transplantation

Acute renal failure (ARF) occurs with significant frequency after myeloablative and nonmyeloablative allogeneic hematopoietic cell transplantation (HCT). Myeloablative (conventional) HCT is the standard of care for cure of various malignant disorders. The newer modality of nonmyeloablative ("mini-allo") HCT is reserved for patients with advanced age and comorbidities who are ineligible for myeloablative HCT. The present study compares the incidence of ARF between patients undergoing concurrent myeloablative and nonmyeloablative HCT in the same period at the same institution. This retrospective cohort study from 1997 to 2003 compares 140 myeloablative and 129 nonmyeloablative patients from the Fred Hutchinson Cancer Research Center. Severity of ARF was classified into 4 grades based on the increase in serum creatinine levels in the first 100 days after HCT. Mortality was studied at 100 days and 1 year. Nonmyeloablative patients were significantly older and had greater pretransplantation comorbidity at baseline. Despite this, patients undergoing myeloablative HCT had a greater incidence of severe ARF (grades 2 and 3, 73% versus 47%; P < 0.001). The incidence of dialysis also was 4-fold greater (12% versus 3%; P < 0.001) in the myeloablative than nonmyeloablative group. On multivariate analysis after controlling for baseline characteristics, myeloablative HCT was associated with a 4.8-fold greater incidence of ARF compared with nonmyeloablative HCT. Nonrelapse mortality also was greater in the myeloablative group at 100 days and 1 year. The incidence and severity of ARF, as well as nonrelapse mortality, occurring after nonmyeloablative HCT is significantly lower compared with myeloablative HCT.

Proximal tubular cytochrome c efflux: Determinant, and potential marker, of mitochondrial injury

Cytochrome c (cyt c) is released from mitochondria after tissue injury, but little is known of its subsequent fate. This study was undertaken to ascertain: (1) does cyt c readily gain access to the extracellular space; (2) if so, what are some determinants of this process; and (3) might cyt c release be a potentially useful marker of in vivo tissue damage. Isolated mouse proximal tubules (PT) were subjected to site 1 (rotenone; Rot), site 2 (antimycin A, AA), or site 3 (hypoxic) respiratory chain blockade (+/- 2 mmol/L glycine, to prevent plasma membrane disruption/cell death). Alternatively, oxidant injury was imposed (Fe(2+) or cholesterol oxidase). Extra- and intracellular cyt c levels were quantified by Western blot. Plasma or urine cyt c levels were also determined after rhabdomyolysis or ischemic acute renal failure (ARF) (in mice), or clinical ARF. AA, Rot, and hypoxia caused variable degrees of PT cyt c release (AA >> rot approximately hypoxia), but at most, <20% of total cell content was involved. In contrast, Fe(2+) evoked approximately 65% cyt c efflux, and cholesterol oxidation caused approximately 100% cyt c release. Glycine did not block cyt c efflux, dissociating this process from plasma membrane disruption/necrotic cell death. After rhabdomyolysis, plasma cyt c levels rose and correlated with the severity of ARF (r, 0.93 vs. BUNs). Cyt c was detected in urine after both experimental and clinical ARF. Cell cyt c release is dependent on the site and the type of mitochondrial injury sustained. Oxidative injury, in general, and cholesterol oxidation, in particular, seem particularly relevant in this regard. After mitochondrial release, cyt c traverses plasma membranes, eventuating in the extracellular space. The data suggest that plasma and/or urine cyt c appearance might function as a clinically useful in vivo marker of mitochondrial stress and the tissue injury sustained.

Resistance to ischemic acute renal failure in the Brown Norway rat: A new model to study cytoprotection

An in vivo model of intrinsic resistance to ischemia could be invaluable to define how specific pathways to injury or putative protectors from injury affect the severity of acute renal failure (ARF). The purpose of this study was to determine whether separate rat strains had differential sensitivity to renal ischemia, characterize the extent of protection, and begin to define differences in gene expression that might impact on the severity of ARF. The sensitivity to 45 minutes of renal ischemia in Sprague-Dawley rat (SD) was compared with 2 lines of Brown-Norway rats (BN/Mcw, BN/Hsd). Constitutive and inducible stress protein expression was compared between strains. At 24 hours' reperfusion, SD rats had higher creatinine (3.4 mg/dL), elevated Na and water excretion, and proximal tubule necrosis. Both strains of BN rats were resistant to loss of renal function (Scr = 0.9 mg/dL at 24 hours' reflow) and had preserved renal morphology. BN rats had no redistribution of Na,K-ATPase into detergent-soluble cortical extracts found early (15 minutes) after ischemia in SD rats. Hsc73 expression did not differ between strains and was not induced by ischemia. Compared with SD, induction of Hsp25 and 72 by renal ischemia was blunted in both BN strains. Constitutive Hsp25 was higher in both BN-Mcw and BN-Hsd compared with SD rat kidney. Constitutive Hsp72 was significantly higher only in BN-Mcw kidneys. Immunohistochemistry showed baseline Hsp72 and 25 expression was increased in proximal tubules of BN-Mcw versus SD. BN rat kidney is resistant to ischemic injury and provides a new model for studying cytoprotective mechanisms. Initial study of strain-specific gene expression suggests particular stress proteins are among the potential mechanisms contributing to protection against ARF.

The Pattern of Acute Renal Failure in Ilorin, Nigeria

Objectives: Acute renal failure is a common cause of morbidity and mortality in Nigeria. The early detection and prompt treatment of acute insults to the kidneys may prevent renal failure which is capital intensive in its management. Majority of Nigerians cannot afford the cost of renal substitution therapy which is scarce and expensive. There is no renal replacement therapy subsidy and the National Health Insurance Scheme is yet to be implemented. These underscore the need for some form of preventive nephrology in order to reduce and possibly avoid renal failure. In line with the foregoing, a 9-year (1990-1998) retrospective appraisal of causes, management and outcome of acute renal failure (ARF) was undertaken in our centre. Methods: All the ARF patients that presented primarily to the nephrology unit or were referred to the unit from other departments of the University of Ilorin Teaching Hospital for intervention were studied. Results: A total of 86 patients (40 males and 46 females) with age range between 3 and 65 years were reviewed. About 79% of the patients were less than 40 years of age and most were females. Sixty three (75%) patients were oliguric at presentation while 23 (26.7%) were non-oliguric. Altered sensorium, vomiting, and hiccups were present in 87%, 40%, and 23% respectively. Severe anaemia that necessitated blood transfusion was present in 41 (48%). The major Aetiological factors were septicaemia (36%), severe gastroenteritis (22%), acute glomerulonephritis (9.3%); drug induced (8%) and obstructive uropathy (6%). Thirteen patients had haemodialysis with 31% mortality, 9 had peritoneal dialysis with a mortality of 67% while 58 were managed conservatively with 64% deaths. The important poor prognostic factors identified were extremes of age, severe infections, late presentation, delayed intervention therapy and underlying/concurrent medical illness. The main factors that influenced the mode of therapy were severity of ARF and financial constraint. Haemodialysis appears to be the preferred method of substitution therapy in our environment for severe ARF. An urgent need for the formation of a National preventive nephrology policy is again reemphasized. Conclusion: A significant number of the patients are under 40 years old. The major causes of renal failure in Ilorin are preventable and treatable conditions. Haemodialysis is the preferred mode of intervention. Key Words: Acute renal failure, causes, management and prognosis Orient Journal of Medicine Vol.15(1&2) 2003: 18-23