Risk Factors For Renal Impairment Research Articles

Antiretroviral therapy, immune suppression and renal impairment in HIV-positive persons

The purpose of this article is to review recent literature on antiretroviral treatment (ART) and immune suppression as risk factors for renal impairment in HIV-positive persons, and to discuss pending research questions within this field. Several individual antiretroviral agents (ARVs) including tenofovir and several protease inhibitors have, in diverse study settings, been associated with renal impairment. Traditional renal risk factors are common among those experiencing adverse renal impairment to ARVs, but do not fully explain why only some develop these effects. Discontinuation of nephrotoxic ARVs is common with declining renal function, but has unknown long-term consequences. Immune suppression is a strong independent risk factor for renal impairment, and ongoing investigations will clarify whether initiating ARVs with nephrotoxic properties at higher CD4 cell counts will have net beneficial effects on renal function. With improvements in survival, multiple risk factors have emerged for renal impairment in HIV-positive persons. Although certain ARVs may cause moderate renal impairment, effects on more severe renal impairment remain unresolved. Regular renal function monitoring allow for switching away from nephrotoxic ARVs in case of decreasing function. If such actions prove beneficial higher prevalence of ARV-associated severe renal impairment may emerge in populations without access to regular monitoring.

Factors Associated With Renal and Urological Complications in Patients Suffering From Spinal Cord Injuries During Subsequent Years of Post-Injury

Virtually all patients with a spinal cord injury (SCI) suffer from neurogenic lower urinary tract dysfunction (NLUTD). The major goal of any treatment of these patients is the preservation of renal function. Especially suprasacral SCI frequently leads to elevated bladder storage pressures which are the major risk factor for renal deterioration. Therefore, the primary objective of bladder management is to achieve low pressure urine storage and emptying. To classify NLUTD of an individual patient and to monitor treatment, regular controls of bladder function are mandatory. The authors assessed the patients with SCI by questionnaires, laboratory tests and imaging. The number of patients included (5901) is impressive. The number of urologic complications observed is rather high. It was not surprising that presence of urologic complications was associated with level of injury and time since injury. It is noteworthy, however, that these complications are depending on the living place (1). Unfortunately, but understandably, no urodynamic data were included in the analysis. It is very demanding to collect urodynamic data from such a large patient cohort. Furthermore, urodynamic examinations are merely possible in specialized centers, and I suspect that this examination was not available for all patients at every control visit. Urodynamics, however, are considered the gold standard for the assessment of the main risk factors for renal damage, namely a detrusor leak point pressure/storage pressure > 40 cm H2O and/or a low detrusor compliance (< 20 mL/cm H2O). Until today, these factors can exclusively be assessed by urodynamics. Thus, it is crucial for the evaluation of NLUTD, since significant changes in NLUTD may occur without symptoms in about 70% of patients with SCI (2). The lack of urodynamic examinations may at least be one explanation for the higher risk for renal complications in SCI patients living in rural areas. As a consequence, the more frequent use of urodynamic testing in this group of patients may in the future even improve the outcome of patients with SCI. As urodynamics are expensive, time consuming, and carry the risk of urinary tract infections, a new diagnostic parameter would be clinically helpful if it either could replace urodynamics or could be used as an additional diagnostic tool to detect SCI patients with NLUTD without risks for consecutive renal damage. Sonographic measurement of the bladder wall thickness may be a future option, but until today, this technique is not well standardized and cannot replace urodynamics yet (3). Not unexpectedly, urinary tract infections are the most common urologic complication in these patients. The frequency of urinary tract infections depends on the method used for bladder evacuation, with indwelling catheters having the highest infection rates. The study does not distinguish between the different methods of bladder management. In general, indwelling catheters should be avoided if ever possible to reduce the number of urinary tract infections (4). In summary, the authors are congratulated for their extensive study, providing the readers with important information about the impact of demographic and environmental factors on urologic complications in SCI patients. As these factors also include the coverage of medical supplies, which is world-wide dependent on living place and social status, the results also mirror the need of optimized diagnostics and treatment of SCI patients as demanded by the world health organization (5). As meticulous urodynamic diagnostics and adequate urologic treatment have been proven to dramatically decrease the rate of urologic complications after SCI (6), the nationwide access to urologic care for patients with SCI should be targeted in the future. Footnotes Financial Disclosure: I have no conflict of interest.

Renal impairment is frequent in chronic hepatitis C patients under triple therapy with telaprevir or boceprevir

In clinical trials with telaprevir (TLV) and boceprevir (BOC) renal impairment was not reported as a relevant adverse event. The PAN study is a noninterventional study enrolling patients treated with peginterferon alfa-2a/ribavirin (PEG/RBV) with or without TVL or BOC. Here we restrict the analysis to hepatitis C virus genotype 1 patients having completed 12 (n = 895) or 24 weeks (n = 591) of treatment. For estimation of glomerular filtration rate (eGFR) the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was chosen. Patients on TLV 38/575 (6.6%) and BOC 10/211 (4.7%) more frequently experienced a decrease in eGFR to <60 mL/min compared to patients on PEG/RBV 1/109 (0.9%) (P < 0.05). Risk factors associated with eGFR <60 mL/min in multiple logistic regression analysis were age (P < 0.001), arterial hypertension (P < 0.05), higher serum creatinine at baseline (P < 0.001), and being on triple therapy with TLV or BOC (P < 0.01). Patients with an eGFR of <60 mL/min had a lower absolute mean hemoglobin at week 12 compared to patients with an eGFR >60 mL/min (9.7 g/dL ± 1.4 g/dL versus 11.0 g/dL ± 1.7 g/dL) (P < 0.001). Most patients on TLV with a decrease of eGFR <60 mL/min showed a marked improvement in renal function after discontinuation of TLV. Renal impairment has not been reported as a safety signal in clinical trials with TVL or BOC. However, in this large cohort including patients with risk factors for renal impairment a marked decline in renal function was observed in about 5% of patients on triple therapy. In addition to being a safety concern, substantial ribavirin dose reductions have to be considered in these patients, as anemia was more pronounced in patients with impaired renal function.

Risk factors for renal impairment in patients with solid tumors or multiple myeloma treated with zoledronic acid

Using retrospective prescription analysis, this study aimed to investigate the risk factors for renal impairment among adult solid tumor and multiple myeloma patients who have received zoledronic acid injections in a teaching hospital over the last 4 years. We examined solid tumor and multiple myeloma patients who had received at least 1 zoledronic acid injection in a teaching hospital in Seoul with at least 2,000 beds over the 4 years between January 2008 and December 2011. The injection histories and serum creatinine levels of these patients were included in the analysis. Patients who developed renal impairment subsequent to zoledronic acid injection were identified, and the risk factors were statistically analyzed. In only 1 case was zoledronic acid injection reduced as directed by the creatinine clearance guidelines. Four patients whose creatinine clearance was less than 30 ml/min were injected with zoledronic acid even though its use is contraindicated in this situation. Of the 338 research subjects, 26 developed renal impairment. The following were confirmed to be statistically significant (p < 0.05) risk factors for the development of renal impairment: serum creatinine (at first injection) of greater than 1.4 mg/dl, diabetes, hypertension, thalidomide prescription, multiple myeloma, and previous pamidronate usage. Based on the results of this study, renal monitoring is necessary following zoledronic acid injection. In addition, for patients with renal impairment risk factors, a risk-benefit analysis must be performed before zoledronic acid is administered, and it must be administered at an appropriate dose according to the level of renal function.

Short-term Administration of Diclofenac Sodium Affects Renal Function After Laparoscopic Radical Nephrectomy in Elderly Patients

Non-steroidal anti-inflammatory drugs decrease the glomerular filtration rate. However, few studies have been conducted on renal function in patients treated with non-steroidal anti-inflammatory drugs during the first week after laparoscopic radical nephrectomy. The purpose of this study is to determine whether short-term administration of non-steroidal anti-inflammatory drugs during the first week after laparoscopic radical nephrectomy is a risk factor for impaired renal function. Renal carcinoma patients undergoing laparoscopic radical nephrectomy in Nagoya University Hospital from April 2004 to July 2010 were identified in a retrospective cohort study. The 164 patients were divided into non-non-steroidal anti-inflammatory drug-treated (n=50) and non-steroidal anti-inflammatory drug-treated (n=114) groups. Elderly patients (>60 years old) in the non-steroidal anti-inflammatory drug-treated group showed a significant correlation between the residual renal function ratio and the total dose of diclofenac sodium (r=-0.277, P<0.05). There was no significant correlation between the residual renal function ratio and the total dose of loxoprofen sodium. The time to doubling of the serum creatinine level was significantly shorter in elderly patients treated with diclofenac sodium compared with that in patients treated with non-non-steroidal anti-inflammatory drugs (P=0.034). These results suggest that renal ischemia induced by short-term administration of diclofenac sodium impairs renal function in elderly patients after laparoscopic radical nephrectomy. In the present study, we found the first evidence that short-term administration of diclofenac sodium is one risk factor for renal impairment after laparoscopic radical nephrectomy in elderly patients. To prevent renal impairment after laparoscopic radical nephrectomy in elderly patients, the use of loxoprofen sodium, which has a negligible effect on renal function compared with diclofenac sodium, is recommended.

Renal Dysfunction is Common Among Adults After Palliation for Previous Tetralogy of Fallot

Long-term survival after tetralogy of Fallot (TOF) repair is excellent. However, little is published regarding late noncardiac complications. This study aimed to determine the prevalence and risk factors for renal dysfunction among adults after TOF repair. For this study, 56 adult patients with complete repair of TOF were identified, and their charts were retrospectively reviewed. An estimated glomerular filtration rate (eGFR) for each patient was calculated using the Modification of Diet in Renal Disease formula (MDRD). Using each patient's eGFR, he or she was classified into stages based on the National Kidney Foundation chronic kidney disease (CKD) staging. Clinical parameters were compared among patients with and those without renal dysfunction to identify risk factors for renal impairment. The median estimated eGFR rate for the cohort was 78 ml/min/1.73 m(2). Based on the National Kidney Foundation CKD staging system, 54 % of the patients had at least stage 2 chronic renal disease. The risk factors identified were hypertension (p < 0.01), type 2 diabetes mellitus (p < 0.05), longer follow-up evaluation (p < 0.005), older age at complete repair (p < 0.05), and use of daily diuretics (p < 0.05). After repair of TOF, renal dysfunction is common at late follow-up evaluation. The study findings show the importance of routine assessment of renal function and the need to limit or avoid future episodes of acute kidney injury in this at-risk population.

News from the International Stroke Conference: New Analysis Shows Diastolic Blood Pressure, Renal Impairment Risk Factors for Intracranial Hemorrhage

News from the International Stroke Conference: New Analysis Shows Diastolic Blood Pressure, Renal Impairment Risk Factors for Intracranial Hemorrhage

Acute kidney injury associated with trimethoprim/sulfamethoxazole

Trimethoprim/sulfamethoxazole effectively treats community-acquired soft tissue infections and urinary tract infections, both of which occur in patients with risk factors for renal impairment. We systematically studied the adverse renal effects of trimethoprim/sulfamethoxazole in a middle-aged veteran population. We reviewed complete electronic records for all patients who, during a 3 year period, had received ≥6 days of treatment with trimethoprim/sulfamethoxazole and for whom a baseline and follow-up determination of serum creatinine and blood urea nitrogen (BUN) were available. Of 573 patients who met inclusion criteria, 64 (11.2%) had increases in both serum creatinine and BUN that met predetermined criteria for acute kidney injury (AKI): in 33 (5.8%), AKI was judged likely due to trimethoprim/sulfamethoxazole; in 28 (4.9%), possibly due to trimethoprim/sulfamethoxazole; and in 3 (0.52%), unrelated to trimethoprim/sulfamethoxazole. Five additional patients (0.9%) had elevations only in serum creatinine. In nearly all cases likely due to trimethoprim/sulfamethoxazole, AKI resolved promptly after discontinuation of therapy, but one patient required dialysis. Pyuria appeared in only 2 of 37 patients who had urinalyses; eosinophiluria was not observed. In a multivariate model, patients with hypertension and diabetes mellitus had increased risk for renal insufficiency, especially if these conditions were considered poorly controlled. In a middle-aged male inpatient population treated for a minimum of 6 days, AKI is much more common with trimethoprim/sulfamethoxazole therapy than previously reported. Intrinsic renal impairment rather than interstitial nephritis or competition for creatinine clearance appears responsible for the great majority of cases, and neither an effect of dose nor duration was detected in a univariate analysis. Impairment is transient if therapy is discontinued.

Diabetic nephropathy and associated risk factors for renal deterioration

Predominantly diabetic nephropathy starts with glomerulosclerosis, when plasma molecules cross the dismantled glomerular basement membrane (GBM) and subsequently appear in urine. Therefore proteinuria is a sensitive criterion to diagnose progressive renal impairment and the presence of immunoglobulin like large molecules is potentially able to predict severity of nephropathy. Directly, or indirectly hyperglycemia induces proteinuria and high urinary excretion of IgG appears with progression of glomerular injury. This is an observational study of 683 patients with type 2 diabetes mellitus. Patients with varying degree of proteinuria were enrolled and classified into three groups according to the urinary albumin creatinine ratio (UACR, 300 mg/g creatinine.) and each group was further sub-classified into the low and high urinary IgG creatinine ratio (UIgGCR) based on the median value. Biochemical parameters were analyzed by standard laboratory methods. The association of proteinuria and odds ratio for risk factors of diabetic nephropathy was estimated using multinomial logistic regression models. The normoalbuminuric and microalbuminuric patients with high UIgGCR had shown lower eGFR (p < 0.05). There was no interaction observed between higher UIgGCR and lower eGFR in regression model analysis. Multinomial logistic regression model estimated the odds ratio for the AGEs, AOPP, lipid hydroperoxides and lipid peroxidation products were increased; 5.64 (95% CI 3.52–9.04), 1.03 (95% CI 1.02–1.04), 2.71 (95% CI 2.05–3.57) and 13.72 (95% CI 6.98–26.95) respectively with high UIgGCR in diabetic patients. High UIgGCR has shown a significant association with decreased eGFR and increased odds for potential hazardous factors. The current study has shown UIgGCR as an increased relative risk, and threat for rapid progression of diabetic nephropathy, possibly because GBM is the primary vulnerable site for deterioration by several hazardous metabolites. In conclusion, association between fractional clearance of IgG and relative risk of GBM threatening factors should be useful for prediction of progressive nature of diabetic nephropathy.

Frequency and risk factors of renal impairment during long‐term adefovir dipivoxil treatment in chronic hepatitis B patients

There are insufficient data on renal safety during long-term adefovir dipivoxil (ADV) treatment. We aimed to elucidate the incidence and risk factors of renal impairment in chronic hepatitis B (CHB) patients treated with ADV. We retrospectively enrolled 687 CHB patients (51.4% with compensated cirrhosis) treated with ADV alone (18.2%) or in combination with lamivudine (81.8%) for more than 12 months. Renal function was measured using the estimated glomerular filtration rate (eGFR), and renal dysfunction was defined as mild (20-30% decrease), moderate (30-50%), or severe (more than 50%). During the median treatment duration of 27 months, 72 patients (10.5%) developed renal impairment, which was mild in 77.8% of cases, moderate in 20.8% of cases, and severe in one patient. The cumulative incidence of renal impairment at 1, 3, and 5 years was 2.6%, 14.8%, and 34.7%, respectively. Modification of the dosing interval or discontinuation of ADV was required in seven and three patients, respectively, and none of them showed a further decline in the eGFR. Although a univariate analysis revealed age, the number of exposure to radio-contrast dye, liver cirrhosis, and hepatocellular carcinoma as risk factors of renal impairment, age was the only significant risk factor identified in the multivariate analysis (odds ratio = 1.048, 95% confidence interval = 1.019-1.076, P = 0.001). Renal impairment in long-term ADV users was relatively frequent, but serious renal toxicity was rare, and all cases were safely managed. Careful monitoring of renal function is required, especially in older patients.

Minimizing contrast medium dose during transapical aortic valve implantation: it is worth the effort

Madershahian et al. [1] have examined a clinically important issue—the influence of contrast media dose on adverse outcomes post-transapical aortic valve implantation (TA-AVI). The authors retrospectively examined 50 TA-AVI patients with an elevated preoperative creatinine (>1.3 mg/dl) and determined that an elevated dose of contrast media (> 100 ml) was associated with higher mortality, as well as a trend towards increased intensive care unit (ICU) length of stay. Although the investigators failed to find that elevated contrast media dose was an independent predictor of mortality, this may have been due to the relatively small sample size of the study. The described association between contrast media dose and adverse outcomes post-TA-AVI is an important finding, but not particularly surprising. Pre-existing renal impairment is a fairly common finding in TA-AVI patients. Such patients have a high incidence of congestive heart failure, peripheral vascular disease, diabetes and hypertension—all known risk factors for renal impairment. Contrast-induced nephropathy may frequently occur in such patients, particularly if they have recently undergone cardiac catheterization or computed tomography. It is for these reasons that we try to maximize the period of time between transcutaneous aortic valve procedures and preoperative contrast-based investigations in patients with pre-existing renal impairment. Acute renal failure post-TA-AVI is a fairly common complication. A previous study from our centre revealed a 16% prevalence of acute kidney injury (AKI), defined as a decrease in estimated glomerular filtration rate of> 50%, in 270 TA-AVI patients [2]. Patients with AKI had increased ICU and hospital lengths of stay. In addition, AKI was an independent risk factor for in-hospital mortality (odds ratio 5.9), and 1-year survival was markedly decreased in AKI patients (45 vs. 80% in patients without AKI, P < 0.001). The administration of more than 90 ml of contrast dye during the TA-AVI procedure was an independent predictor of postoperative AKI. We concluded that contrast media dose should be minimized during TA-AVI in order to decrease the risk of postoperative renal failure. Acute renal failure can occasionally lead to multiple complications, such as respiratory insufficiency, intubation, prolonged intensive care stay and even mortality in TA-AVI patients, probably because of their pre-existing comorbidities and reduced physiological reserve. Acute renal insufficiency post-cardiac surgery most frequently arises on postoperative days 1–3, and may occur without any recognizable preceding factors [3]. The occurrence of AKI with the abovementioned cascade of complications can be particularly vexing in patients with a heretofore completely uncomplicated TA-AVI procedure. The main drawback of the study from Madershahian et al. [1] is the inability to determine if the relation between increased contrast media and worse post-TAVI outcomes is associative or causative. That is, was the increased contrast media dose a consequence of a complicated TAVI procedure that subsequently lead to worse outcomes, or did the contrast media in and of itself lead to renal failure and subsequent morbidity and mortality? The longer operative time in the high contrast media dose group would suggest that these patients experienced a more complicated intraoperative course, although this may also be explained by their operations being performed in the earlier part of the operators’ learning curve. Unfortunately, the authors were unable to assess for other possible markers of procedure complexity including valve deployment difficulties, coronary obstruction, catecholamine requirement or low cardiac output syndrome. In addition, patients who received a higher contrast media dose had a higher risk preoperative profile, including prevalence of coronary disease and EuroSCORE predicted risk of mortality, further complicating interpretation of the results. However, the authors’ conclusion that excessive contrast media usage should be avoided in patients with pre-existing renal impairment seems prudent and logical. Some investigators have reported that TA-AVI procedures can be performed with the administration of minimal or no contrast media [4]. The potential beneficial effects of contrast media avoidance, however, need to be weighed against the risk of possible difficulties in precise valve positioning during deployment. Although complete elimination of contrast media may not be feasible in the majority of the TA-AVI patients, contrast dose minimization is a reasonable and worthy goal. In addition, awareness of the nephrotoxic effects of contrast media within the cardiac surgery community needs to be

Reducing renal failure: how low do glucose levels need to go?

SUMMARY Diabetic kidney disease is the commonest cause of end-stage kidney disease worldwide. One strategy to prevent the development and progression of diabetic kidney disease is intensive blood glucose control. Randomized controlled trials such as the UKPDS and DCCT have demonstrated that a target HbA1c level of 7% improves renal outcomes. More recently, ACCORD, ADVANCE and VADT have explored the effects of targeting even lower HbA1c levels of 6.0–6.5%. These contemporary trials have universally reported improvements in albuminuria but no clear effects on preventing end-stage kidney disease. Thus, the additional and likely long-term renal benefits of intensive glucose lowering to achieve HbA1c levels ≤7% need to be balanced against the potential risks of intensive therapy such as severe hypoglycemia. An individualized approach is required with the understanding that the greatest renal benefits are likely to be achieved at a HbA1c level of ≤7%. Other risk factors for renal impairment should also be addre...

Factors Associated with the Decline of Kidney Function Differ among eGFR Strata in Subjects with Type 2 Diabetes Mellitus

Introduction. There is no report about risk factors for renal deterioration according to the clinical stage, divided by the estimated glomerular filtration rate (eGFR) in type 2 diabetes. Materials and Methods. We evaluated the factors correlated with the annual eGFR decline in 1303 subjects with type 2 diabetes whose eGFR was ≥30 mL/min/1.73 m2. eGFR strata were defined by baseline eGFR value as follows: stratum 1: ≥90, stratum 2: ≥60, <90, and stratum 3: ≥30, <60. Results. The annual eGFR decline was 2.3 ± 5.4 mL/min/1.73 m2 in overall subjects. Multiple linear regression analysis demonstrated that age, male sex, systolic blood pressure, logarithmically transformed albumin excretion rate (AER), eGFR strata, and hemoglobin concentration were significantly correlated with the annual eGFR decline. When stratified by eGFR, the factors that showed a significant correlation were different among eGFR strata. AER was significantly correlated with annual eGFR decline in all eGFR strata. Hemoglobin concentration showed a significant correlation only in the advanced eGFR stratum. Conclusion. The factors correlated with the annual eGFR decline were different among eGFR strata in type 2 diabetes mellitus, and hemoglobin concentration and AER were important factors for renal deterioration, especially in the advanced eGFR stratum.

The association between renal tubular damage and rapid renal deterioration in the Japanese population: the Takahata study

Injury to renal tubules plays an important role in the development of various renal diseases; however, the prevalence and significance of renal tubular damage in the general population are unclear. To clarify this point, we conducted a community-based study, using urinary β(2)-microglobulin as a marker of tubular damage. The subjects studied were 3,444 Japanese over the age of 40years. The urinary β(2)-microglobulin-creatinine ratio (UBCR) was assessed in morning spot urine samples. In this population, the distribution of the UBCR among these subjects was skewed towards higher values and a high UBCR (≥300μg/g) was identified in 438 (12.7%) subjects. However, overlap with macroalbuminuria and renal insufficiency [estimated glomerular filtration rate (eGFR) <60mL/min/1.73m(2)] was observed in only 25 (5.7%) and 58 (13.2%) of these subjects, respectively. Multivariate analysis indicated that a high UBCR was positively associated with aging, hypertension, macroalbuminuria and increased urinary sodium excretion. A 5-year longitudinal analysis in 899 subjects indicated a greater decline in eGFR in parallel with the increase in baseline UBCR. After adjustment for possible confounders, a high UBCR was an independent risk factor for rapid decline in eGFR [<-10mL/min/1.73m(2); odds ratio 1.79 (95% confidence interval 1.07-2.99), P=0.026]. This study showed that renal tubular damage was common and was an independent risk factor for renal deterioration in the Japanese population. More attention should be paid to occult renal tubular damage in order to prevent end-stage renal disease.

Reduced Methotrexate Clearance and Renal Impairment in a Boy With Osteosarcoma and Earlier Undetected Autosomal Dominant Polycystic Kidney Disease (ADPKD)

We report a 12-year-old boy with osteoblastic osteosarcoma of the right femur. He was started on chemotherapy according to the EURAMOS/COSS 1 protocol. Chemotherapy with doxorubicin/cisplatin resulted in reversible acute renal failure and methotrexate levels were repeatedly elevated. Family history suggested an autosomal dominant polycystic kidney disease. Genetic testing revealed a novel mutation c.10707_10712del (p.Val3569_3570del) in exon 36 of the PKD1 gene. Patients with autosomal dominant polycystic kidney disease may be at risk for acute renal failure during chemotherapy without signs of renal impairment. A careful family history is important to exclude risk factors for renal impairment before introducing high-dose chemotherapy.

Risk factors for the development of albuminuria and renal impairment in type 2 diabetes--the Swedish National Diabetes Register (NDR)

The aim of this study was to identify clinical risk factors associated with the development of albuminuria and renal impairment in patients with type 2 diabetes (T2D). In addition, we evaluated if different equations to estimate renal function had an impact on interpretation of data. This was done in a nationwide population-based study using data from the Swedish National Diabetes Register. Three thousand and six hundred sixty-seven patients with T2D aged 30-74 years with no signs of renal dysfunction at baseline (no albuminuria and eGFR >60 mL/min/1.73 m(2) according to MDRD) were followed up for 5 years (2002-2007). Renal outcomes, development of albuminuria and/or renal impairment [eGFR < 60 mL/min/1.73 m(2) by MDRD or eCrCl > 60 mL/min by Cockgroft-Gault (C-G)] were assessed at follow-up. Univariate regression analyses and stepwise regression models were used to identify significant clinical risk factors for renal outcomes. Twenty percent of patients developed albuminuria, and 11% renal impairment; thus, ~6-7% of all patients developed non-albuminuric renal impairment. Development of albuminuria or renal impairment was independently associated with high age (all P < 0.001), high systolic BP (all P < 0.02) and elevated triglycerides (all P < 0.02). Additional independent risk factors for albuminuria were high BMI (P < 0.01), high HbA1c (P < 0.001), smoking (P < 0.001), HDL (P < 0.05) and male sex (P < 0.001), and for renal impairment elevated plasma creatinine at baseline and female sex (both P < 0.001). High BMI was an independent risk factor for renal impairment when defined by MDRD (P < 0.01), but low BMI was when defined by C-G (P < 0.001). Adverse effects of BMI on HbA1c, blood pressure and lipids accounted for ~50% of the increase risk for albuminuria, and for 41% of the increased risk for renal impairment (MDRD). Distinct sets of risk factors were associated with the development of albuminuria and renal impairment consistent with the concept that they are not entirely linked in patients with type 2 diabetes. Obesity and serum triglycerides are semi-novel risk factors for development of renal dysfunction and BMI accounted for a substantial proportion of the increased risk. The equations used to estimate renal function (MDRD vs. C-G) had an impact on interpretation of data, especially with regard to body composition and gender.

Three cases of severe metformin-related lactic acidosis

The American Diabetes Association and the European Association for the Study of Diabetes published a consensus statement on the approach to hyperglycaemia in individuals with type 2 diabetes.1 In accordance with this statement, metformin is widely prescribed, as it is the first-line drug for type 2 diabetes treatment. Lactic acidosis incidence during metformin therapy is estimated to be two to nine cases per 100 000 patients per year, an incidence not too different from that reported in patients with type 2 diabetes who do not take metformin.2 In fact, there is some controversy concerning the association between metformin and lactic acidosis. Metformin does not seem to be the initial cause of lactic acidosis but could, possibly, precipitate the acid–base imbalance and contribute to the severity of the acidosis.3 The risk factors for metformin-related lactic acidosis include decreased renal, cardiac and hepatic functions and/or suspected tissue hypoxia. On the contrary, in recent years, several cases of severe lactic acidosis have been reported in the literature, even in the absence of these risk factors. Medical therapy for metformin-associated lactic acidosis includes management of concurrent diseases; mechanical ventilation to prevent muscle fatigue, to help to maintain respiratory compensation for metabolic acidosis and to optimize oxygenation; bicarbonate haemodialysis or continuous veno-venous haemofiltration (CVVH) to decrease the metformin level and correct acidosis; and intensive vasoactive support with norepinephrine or epinephrine. The use of bicarbonate is known to worsen intracellular acidosis and hyperlactacidaemia and remains controversial. In the last 14 months, three patients undergoing chronic metformin therapy have been admitted to our critical care unit for severe lactic acidosis (Table 1).Table 1: Patient characteristicsAll patients we saw were hypothermic with a high Simplified Acute Physiology Score II (SAPS II) score at admission. Two patients required high doses of epinephrine due to hypotension refractory to norepinephrine–dobutamine association. Liver function was never affected. Patient 1 and patient 2 had risk factors for lactic acidosis, as they had mild and moderate previous elevation of creatinine level, respectively; in these cases, metformin should be withdrawn. Patient 3 had no contraindication to metformin use.4 Two out of three had a mild infection before admission (patients 1 and 3). Diabetic nephropathy often develops insidiously. Moreover, infection or dehydration can rapidly lead to renal function impairment. Cohen and Woods divided lactic acidosis into two categories. Type A is lactic acidosis occurring in association with clinical evidence of poor tissue perfusion or oxygenation, whereas type B occurs when no clinical evidence of poor tissue perfusion or oxygenation exists. All three patients had developed acute renal failure, a known cause of type B lactic acidosis. Two patients had infections, which may also have contributed to tissue hypoxia and type A lactic acidosis. Regardless of the type of lactic acidosis in our patients, the incidence of metformin toxicity can be reduced with close monitoring of renal function. Serum creatinine should be checked at least annually, and probably more often in patients with exposure to risk factors for renal impairment.5 These cases suggest a high index of suspicion for metformin-associated lactic acidosis in older patients, a prompt metformin withdrawal during periods of suspected tissue hypoxia or impaired renal function and the importance of giving patients full information about this side-effect. We have outlined the importance of taking into account risk factors for lactic acidosis and contraindications in prescribing metformin. We also would like to emphasize that, despite the severity of clinical presentation, two patients had an excellent recovery.

Renal Impairment Following Total Joint Arthroplasty: Who Is at Risk?

Postoperative renal impairment is a serious complication of major surgeries that leads to increased morbidity and mortality. The objective of our study was to identify the risk factors for renal impairment following total joint arthroplasty. Among 17 938 total joint arthroplasties performed between 2000 and 2007, patients developing renal complications were identified. For performing univariate and multivariate analyses, patients with renal impairment were matched in a 1:2 ratio with control group who did not develop renal impairment. Ninety-eight (0.55%) patients developed either acute renal failure or acute renal injury. We identified the following as independent risk factors: elevated body mass index; elevated preoperative serum creatinine; and history of chronic obstructive pulmonary disease, liver disease, congestive heart failure, hypertension, and underlying heart disease. Renal impairment was significantly associated with increased duration of hospital stay and with in-hospital and 1-year all-cause mortality. In high-risk patients, preoperative optimization might be considered in an attempt to reduce the incidence of such a complication.

Risk factors for renal function impairment in a series of 502 patients born with spinal dysraphisms

To evaluate the risk of renal damage in a large series of patients affected by spinal dysraphism. Renal function was studied in 502 spinal dysraphisms treated over the last 25 years in a single center: 283 meningomyelocele (MMC), 90 caudal regression syndrome (CRS) and 129 spinal lipoma (SL) cases. In patients with normal and impaired renal function, we compared congenital renal anomalies, vesicoureteric reflux, bladder voiding pattern and upper tract dilatation, analyzing the results with the Fisher test. Neuropathic bladder was observed in 97% of MMC, 60% of CRS, and 39% of SL cases. There was some degree of renal function impairment in 19 MMC (6.7%), 11 CRS (12%, increased to 20% if considering only neuropathic bladder patients), and two SL (1.5%) cases. Renal agenesis was more frequent in CRS (13%), but was not associated with decreased renal function. Overall, vesicoureteric reflux and upper tract dilatation were more frequent in patients with renal damage. Insufficient bladder voiding was statistically associated with renal damage only in the CRS population. Intermittent catheterization did not represent a protective factor against renal damage in patients able to void without significant residual urine. This study has increased our understanding of the prognostic risk factors for renal deterioration. More prospective studies are necessary to confirm these results and correlate treatment with renal outcome.

Reference Range of Urinary Neutrophil Gelatinase-Associated Lipocalin in Very Low-Birth-Weight Infants: Preliminary Data

We sought to determine the reference range for urinary neutrophil gelatinase-associated lipocalin (UNGAL) in very low-birth-weight (VLBW) infants with uncomplicated clinical courses. Samples of urine from 53 VLBW infants between 3 and 28 days of life were prospectively collected weekly for measurement of UNGAL. A subset of 22 infants with uncomplicated medical courses without risk factors for renal impairment was selected for study. Mean +/- standard deviation and range for birth weight and gestational age of study infants were 1156 +/- 191, 790 to 1440 g and 29 +/- 2, 27 to 33 weeks, respectively. The 95th and 99th percentiles for UNGAL concentration from this group of infants were 25 ng/mL and 75 ng/mL, respectively. Bootstrapped mean 95th and 99th percentile values and their standard errors and 95 percent confidence intervals in ng/mL were 33.1 +/- 13.0 (7.7, 58.6) and 67.5 +/- 15.1 (37.9, 97.1), respectively. These values fall within the adult reference range. UNGAL values were stable across the ranges of gestational and postnatal age of the study infants. A preliminary reference range for UNGAL in VLBW infants has been established. Further investigation with more frequent urine collections in a larger population of VLBW infants that includes those with birth weights < 750 g and gestational ages < 27 weeks is necessary to confirm this reference range.