Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy.

BACKGROUND: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. METHODS: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m2 of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. RESULTS: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P = 0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority). Among patients in remission who tested positive for anti-phospholipase A2 receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P = 0.06). CONCLUSIONS: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, NCT01180036.).

Comparison of treatment options in adults with frequently relapsing or steroid-dependent minimal change disease.

BACKGROUND: Studies comparing all treatment options for frequently-relapsing/steroid-dependent (FR/SD) minimal change disease (MCD) in adults are lacking. METHODS: Medical records of 76 adults with FR/SD MCD who were treated with corticosteroids as the first-line therapy were reviewed. Treatment options were compared for the time to relapse, change of therapy and progression (relapse on full-dose treatment). RESULTS: Second-line treatments included rituximab (RTX; n = 13), mycophenolate mofetil (MMF; n = 12), calcineurin inhibitors (CNI; n = 26) and cyclophosphamide (CTX; n = 16). During the second-line treatments, 48 (71.6%) patients relapsed at median 17 (range 2-100) months. The majority of relapses occurred during dose tapering or off drug. Twenty of 65 (30.8%) changed therapy after the first relapse. The median time to relapse after the second line was 66 versus 28 months in RTX versus non-RTX groups (P = 0.170). The median time to change of treatment was 66 and 44 months, respectively (P = 0.060). Last-line treatment options included RTX (n = 8), MMF (n = 4), CNI (n = 3) and CTX (n = 2). Seven (41.2%) patients had a relapse during the last-line treatment at median 39 (range 5-112) months. The median time to relapse was 48 versus 34 months in the RTX versus non-RTX groups (P = 0.727). One patient in the RTX group died presumably of heart failure. No major adverse event was observed. During the median follow-up of 81 (range 9-355) months, no patients developed end-stage renal disease. CONCLUSIONS: Relapse is frequent in MCD in adults. Patients treated with RTX may be less likely to require a change of therapy and more likely to come off immunosuppressive drugs.

Treatment of fibrillary glomerulonephritis with rituximab: a 12-month pilot study.

BACKGROUND: Fibrillary glomerulonephritis (FGN) is a rare type of glomerulonephritis with poor prognosis, with no known effective therapies available for treatment. The objective of the study was to evaluate the efficacy and safety of rituximab in treatment of patients with FGN and to investigate the effect of rituximab on DNAJB9 levels. METHODS: This was a pilot prospective clinical trial in which patients with idiopathic FGN were treated with two courses of rituximab (1 g each) 2 weeks apart at the beginning and then again at 6 months. Primary outcome was defined as preservation of kidney function at 12 months with stable or increased creatinine clearance. Secondary outcome was defined as achieving complete remission (CR) defined as proteinuria <300 mg/24 h or partial remission (PR) with proteinuria <3 g/24 h and at least 50% reduction in the proteinuria. DNAJB9 levels were also measured in the serum at baseline, 6 and 12 months. RESULTS: The creatinine clearance did not change significantly during this time, from 47.7 mL/min/1.73 m2 at baseline to 43.7 mL/min/1.73 m2 during follow-up (P = 0.15). Proteinuria declined from 4.43 (1.6-5.53) g/24 h at baseline to 1.9 (0.46-5.26) g/24 h at 12 months but did not reach significance (P = 0.06). None of the patients reached CR, and 3 of the 11 achieved PR. There was no change in the DNAJB9 levels following treatment with rituximab. The most common adverse event was nasal congestion, fatigue and muscle cramps. CONCLUSIONS: Treatment of patients with two courses of rituximab over a span of 6 months was associated with stabilization of renal function but did not result in a significant change in proteinuria and with no change in the DNAJB9 levels.

Subtyping Hyperchloremia among Hospitalized Patients by Machine Learning Consensus Clustering.

Background and Objectives: Despite the association between hyperchloremia and adverse outcomes, mortality risks among patients with hyperchloremia have not consistently been observed among all studies with different patient populations with hyperchloremia. The objective of this study was to characterize hyperchloremic patients at hospital admission into clusters using an unsupervised machine learning approach and to evaluate the mortality risk among these distinct clusters. Materials and Methods: We performed consensus cluster analysis based on demographic information, principal diagnoses, comorbidities, and laboratory data among 11,394 hospitalized adult patients with admission serum chloride of >108 mEq/L. We calculated the standardized mean difference of each variable to identify each cluster's key features. We assessed the association of each hyperchloremia cluster with hospital and one-year mortality. Results: There were three distinct clusters of patients with admission hyperchloremia: 3237 (28%), 4059 (36%), and 4098 (36%) patients in clusters 1 through 3, respectively. Cluster 1 was characterized by higher serum chloride but lower serum sodium, bicarbonate, hemoglobin, and albumin. Cluster 2 was characterized by younger age, lower comorbidity score, lower serum chloride, and higher estimated glomerular filtration (eGFR), hemoglobin, and albumin. Cluster 3 was characterized by older age, higher comorbidity score, higher serum sodium, potassium, and lower eGFR. Compared with cluster 2, odds ratios for hospital mortality were 3.60 (95% CI 2.33-5.56) for cluster 1, and 4.83 (95% CI 3.21-7.28) for cluster 3, whereas hazard ratios for one-year mortality were 4.49 (95% CI 3.53-5.70) for cluster 1 and 6.96 (95% CI 5.56-8.72) for cluster 3. Conclusions: Our cluster analysis identified three clinically distinct phenotypes with differing mortality risks in hospitalized patients with admission hyperchloremia.

Calcium-phosphate product and its impact on mortality in hospitalized patients.

AIM: This study aimed to assess the relationship between admission Calcium-phosphate (CaP) and in-hospital mortality in hospitalized patients. METHODS: All adult hospitalized patients who had both admission serum calcium and phosphate levels available between years 2009 and 2013 were enrolled. Admission CaP was categorized based on its distribution into six groups (<21, 21-<27, 27-<33, 33 39, 39-<45 and ≥45 mg2 /dL2 ). Multivariate logistic regression was used to assess the association between admission CaP and in-hospital mortality, using the CaP of 27-<33 mg2 /dL2 as the reference group. RESULTS: Abut 14 772 patients were included in the analysis. The association between CaP and in-hospital mortality was U-shaped with the lowest in-hospital mortality in CaP of 27-<33 mg2 /dL2 . After adjusting for potential confounders, both CaP <21 and ≥39 mg2 /dL2 were associated with higher in-hospital mortality. Subgroup analysis demonstrated that the highest in-hospital mortality risk in both chronic kidney disease (CKD) and non-CKD patients occurred when CaP ≥ 45 mg2 /dL2 . CONCLUSION: CaP levels on admission were associated with in-hospital mortality. Highest mortality risk was observed in hospitalized patients with admission CaP of ≥45 mg2 /dL2 in both CKD and non-CKD patients.

Serum Potassium Levels at Hospital Discharge and One-Year Mortality among Hospitalized Patients.

Background and Objectives: The optimal range of serum potassium at hospital discharge is unclear. The aim of this study was to assess the relationship between discharge serum potassium levels and one-year mortality in hospitalized patients. Materials and Methods: All adult hospital survivors between 2011 and 2013 at a tertiary referral hospital, who had available admission and discharge serum potassium data, were enrolled. End-stage kidney disease patients were excluded. Discharge serum potassium was defined as the last serum potassium level measured within 48 hours prior to hospital discharge and categorized into ≤ 2.9, 3.0-3.4, 3.5-3.9, 4.0-4.4, 4.5-4.9, 5.0-5.4 and ≥ 5.5 mEq/L. A Cox proportional hazards analysis was performed to assess the independent association between discharge serum potassium and one-year mortality after hospital discharge, using the discharge potassium range of 4.0-4.4 mEq/L as the reference group. Results: Of 57,874 eligible patients, with a mean discharge serum potassium of 4.1 ± 0.4 mEq/L, the estimated one-year mortality rate after discharge was 13.2%. A U-shaped association was observed between discharge serum potassium and one-year mortality, with the nadir mortality in the discharge serum potassium range of 4.0-4.4 mEq/L. After adjusting for clinical characteristics, including admission serum potassium, both discharge serum potassium ≤ 3.9 mEq/L and ≥ 4.5 mEq/L were significantly associated with increased one-year mortality, compared with the discharge serum potassium of 4.0-4.4 mEq/L. Stratified analysis based on admission serum potassium showed similar results, except that there was no increased risk of one-year mortality when discharge serum potassium was ≤ 3.9 mEq/L in patients with an admission serum potassium of ≥ 5.0 mEq/L. Conclusion: The association between discharge serum potassium and one-year mortality after hospital discharge had a U-shaped distribution and was independent of admission serum potassium. Favorable survival outcomes occurred when discharge serum potassium was strictly within the range of 4.0-4.4 mEq/L.

Impact of Changes in Serum Calcium Levels on In-Hospital Mortality.

Background and objectives: Calcium concentration is strictly regulated at both the cellular and systemic level, and changes in serum calcium levels can alter various physiological functions in various organs. This study aimed to assess the association between changes in calcium levels during hospitalization and mortality. Materials and Methods: We searched our patient database to identify all adult patients admitted to our hospital from January 1st, 2009 to December 31st, 2013. Patients with ≥2 serum calcium measurements during the hospitalization were included. The serum calcium changes during the hospitalization, defined as the absolute difference between the maximum and the minimum calcium levels, were categorized into five groups: 0-0.4, 0.5-0.9, 1.0-1.4, 1.5-1.9, and ≥2.0 mg/dL. Multivariable logistic regression was performed to assess the independent association between calcium changes and in-hospital mortality, using the change in calcium category of 0-0.4 mg/dL as the reference group. Results: Of 9868 patients included in analysis, 540 (5.4%) died during hospitalization. The in-hospital mortality progressively increased with higher calcium changes, from 3.4% in the group of 0-0.4 mg/dL to 14.5% in the group of ≥2.0 mg/dL (p < 0.001). When adjusted for age, sex, race, principal diagnosis, comorbidity, kidney function, acute kidney injury, number of measurements of serum calcium, and hospital length of stay, the serum calcium changes of 1.0-1.4, 1.5-1.9, and ≥2.0 mg/dL were significantly associated with increased in-hospital mortality with odds ratio (OR) of 1.55 (95% confidence interval (CI) 1.15-2.10), 1.90 (95% CI 1.32-2.74), and 3.23 (95% CI 2.39-4.38), respectively. The association remained statistically significant when further adjusted for either the lowest or highest serum calcium. Conclusion: Larger serum calcium changes in hospitalized patients were progressively associated with increased in-hospital mortality.

Serum levels of DNAJB9 are elevated in fibrillary glomerulonephritis patients.

Fibrillary glomerulonephritis (FGN) is a rare glomerular disease. Kidney biopsy is required to establish the diagnosis. Recent studies have identified abundant glomerular deposition of DNAJB9 as a unique histological marker of FGN. We developed an immunoprecipitation-based multiple reaction monitoring method to measure serum levels of DNAJB9. We detected a 4-fold higher abundance of serum DNAJB9 in FGN patients when compared to controls, including patients with other glomerular diseases. Serum DNAJB9 levels were also negatively associated with estimated glomerular filtration rate in patients with FGN. Serum DNAJB9 levels accurately predicted FGN with moderate sensitivity (67%) and with high specificity (98%) and positive and negative predictive value (89% and 95%, respectively). A receiver operating curve analysis demonstrated an AUC of 0.958. These results suggest that serum levels of DNAJB9 could be a valuable marker to predict FGN, with the potential to complement kidney biopsy for the diagnosis of FGN.

Congophilic Fibrillary Glomerulonephritis: A Case Series.

RATIONALE & OBJECTIVE: Congo Red positivity with birefringence under polarized light has traditionally permitted classification of organized glomerular deposits as from amyloid or nonamyloid diseases. The absence of congophilia has been used to differentiate fibrillary glomerulonephritis (GN) from amyloidosis. We describe a series of fibrillary GN cases in which the deposits are Congo Red-positive (congophilic fibrillary GN) and discuss the role of DNAJB9 in distinguishing congophilic fibrillary GN from amyloidosis. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Analysis of the clinicopathologic characteristics of 18 cases of congophilic fibrillary GN. Mass spectrometry was performed and compared with 24 cases of Congo Red-negative fibrillary GN, 145 cases of amyloidosis, and 12 apparently healthy individuals. DNAJB9 immunohistochemistry was obtained for a subset of cases. RESULTS: The proteomic signature of amyloid was not detected using mass spectrometry among cases of congophilic fibrillary GN. DNAJB9, a recently discovered proteomic marker for fibrillary GN, was detected using mass spectrometry in all cases of fibrillary GN regardless of congophilia and was absent in cases of amyloidosis and in healthy individuals. DNAJB9 immunohistochemistry confirmed the mass spectrometry findings. The congophilic fibrillary GN cases included 11 men and 7 women with a mean age at diagnosis of 65 years. Concomitant monoclonal gammopathy, hepatitis C virus infection, malignancy, or autoimmune disease was present in 35%, 22%, 17%, and 11% of patients, respectively. No patient had evidence of extrarenal amyloidosis. Patients presented with proteinuria (100%), nephrotic syndrome (47%), hematuria (78%), and chronic kidney disease (83%). After a mean follow-up of 23 months, 31% of patients progressed to end-stage kidney disease and the remaining 69% had persistently reduced kidney function. LIMITATIONS: Retrospective nature. Blinded pathology evaluations were not performed. CONCLUSIONS: The congophilic properties of organized fibrillary deposits should not be solely relied on in differentiating fibrillary GN from renal amyloidosis. Mass spectrometry and DNAJB9 immunohistochemistry can be useful in making this distinction.

Admission calcium levels and risk of acute kidney injury in hospitalised patients.

BACKGROUND: The risk of acute kidney injury (AKI) development among hospitalised patients with elevated calcium levels on admission remains unclear. The aim of this study was to assess the risk of AKI in hospitalised patients stratified by various admission serum calcium levels. METHODS: This is a single-centre retrospective study conducted at a tertiary referral hospital. All hospitalised adult patients who had admission calcium levels available between 2009 and 2013 were enrolled. Admission calcium was categorised based on its distribution into six groups (≤7.9, 8.0-8.4, 8.5-8.9, 9.0-9.4, 9.5-9.9, and ≥10.0 mg/dL). The primary outcome was hospital-acquired AKI. Logistic regression analysis was performed to obtain the odds ratio of AKI for various admission calcium strata using calcium levels of 8.0-8.4 mg/dL (lowest incidence of AKI) as the reference group. RESULTS: A total of 12 784 patients were studied. Hospital-acquired AKI occurred in 1779 (13.9%) patients. The incidence of AKI among patients with admission calcium ≤7.9, 8.0-8.4, 8.5-8.9, 9.0-9.4, 9.5-9.9 and ≥10 mg/dL was 14.7%, 11.7%, 11.8%, 14.6%, 15.8% and 17.3%, respectively. After adjusting for potential confounders, admission calcium levels ≤7.9, 9.0-9.4, 9.5-9.9 and ≥10 mg/dL were associated with increased risk of AKI with odds ratios of 1.36 (95%CI 1.08-1.72), 1.29 (95%CI 1.08-1.56), 1.38 (95%CI 1.14-1.68) and 1.51 (95%CI 1.19-1.91), respectively. CONCLUSION: Admission hypocalcaemia and hypercalcaemia are associated with an increased risk for hospital acquired AKI. Patients with admission hypercalcaemia (≥10 mg/dL) carry a 1.51-fold risk for AKI development during hospitalisation.

Impact of admission serum calcium levels on mortality in hospitalized patients.

OBJECTIVES: To assess the relationship between admission serum calcium levels and in-hospital mortality in all hospitalized patients. METHODS: All adult hospitalized patients who had admission serum calcium levels available between years 2009 and 2013 were enrolled. Admission serum calcium was categorized based on its distribution into six groups (<7.9, 7.9 to <8.4, 8.4 to <9.0, 9.0 to <9.6, 9.6 to <10.1, and ≥10.1 mg/dL). The odds ratio (OR) of in-hospital mortality by admission serum calcium, using the calcium category of 9.6-10.1 mg/dL as the reference group, was obtained by logistic regression analysis. RESULTS: 18,437 patients were studied. The lowest incidence of in-hospital mortality was associated with admission serum calcium within 9.6 to <10.1 mg/dL. A higher in-hospital mortality rate was observed in patients with serum calcium <9.6 and ≥10.1 mg/dL. Also, 38% and 33% of patients with admission serum calcium <7.9 and ≥10.1 mg/dL were on calcium supplements before admission, respectively. After adjusting for potential confounders, both serum calcium <8.4 and ≥10.1 mg/dL were associated with an increased risk of in-hospital mortality with ORs of 2.86 [95% confidence interval (CI) 1.98-4.17], 1.74 (95% CI 1.21-2.53), and 1.69 (95% CI 1.10-2.59) when serum calcium were within <7.9, 7.9 to <8.4, and ≥10.1 mg/dL, respectively. CONCLUSION: Hypocalcemia and hypercalcemia on admission were associated with in-hospital mortality. Highest mortality risk is observed in patients with admission hypocalcemia (<7.9 mg/dL). One-third of patients with hypercalcemia on admission were on calcium supplements.

The effects of short sleep duration on proteinuria and chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: The risks of proteinuria and chronic kidney disease (CKD) in adults who regularly have short sleep duration (short sleepers) are controversial. The aim of this meta-analysis was to assess the effects of short sleep duration on proteinuria and CKD. METHODS: A literature search was conducted using MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews from the inception of the databases through November 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risks of proteinuria and CKD in short sleepers were included. Pooled risk ratios (RR) and 95% confidence intervals (CI) were computed utilizing a random-effect, generic inverse variance method. RESULTS: Six observational studies with 252 075 individuals and three observational studies with 37 197 individuals were included in the analyses to assess the risks of CKD and proteinuria in short sleepers, respectively. The pooled RR of CKD in short sleepers was 1.51 (95% CI, 0.99-2.55). When meta-analysis was restricted only to studies with adjusted analysis for confounders assessing the risk of CKD in short sleepers, the pooled RR of CKD was 1.54 (95% CI, 0.80-2.95). The pooled RR of proteinuria in short sleepers was 1.47 (95% CI, 1.26-1.72). CONCLUSIONS: Despite the lack of significant association between short sleep duration and CKD, our meta-analysis suggests a potential association between short sleep duration and proteinuria, a surrogate marker for kidney disease progression. Future study is required to investigate if reversal of short sleep helps reduce proteinuria.

Short-Term Tolvaptan Increases Water Intake and Effectively Decreases Urinary Calcium Oxalate, Calcium Phosphate and Uric Acid Supersaturations.

PURPOSE: Some patients cannot effectively increase water intake and urine volume to prevent urinary stones. Tolvaptan, a V2 receptor antagonist, blocks water reabsorption in the collecting duct and should decrease urinary supersaturation of stone forming solutes, although this action has never been proved. MATERIALS AND METHODS: We conducted a double-blind, randomized, placebo controlled, crossover study of 21 calcium urinary stone formers stratified into majority calcium oxalate (10 patients) and calcium phosphate (11) groups. Patients received 45 mg tolvaptan per day or placebo for 1 week, followed by a washout week and crossover to tolvaptan or placebo for week 3. A 24-hour urine sample was collected at the end of weeks 1 and 3. RESULTS: Tolvaptan vs placebo decreased urinary osmolality (mean ± SD 204 ± 96 vs 529 ± 213 mOsm/kg, p <0.001) and increased urinary volume (4.8 ± 2.9 vs 1.8 ± 0.9 L, p <0.001). The majority of urinary solute excretion rates, including sodium and calcium, did not change significantly, although oxalate secretion increased slightly (from mean ± SD 15 ± 8 to 23 ± 8 mg per 24 hours, p = 0.009). Mean ± SD urinary calcium oxalate supersaturation (-0.01 ± 1.14 vs 0.95 ± 0.87 dG, p <0.001), calcium phosphate supersaturation (-1.66 ± 1.17 vs -0.13 ± 1.02 dG, p <0.001) and uric acid supersaturation (-2.05 ± 4.05 vs -5.24 ± 3.12 dG, p = 0.04) all dramatically decreased. Effects did not differ between the calcium oxalate and calcium phosphate groups (p >0.05 for all interactions). CONCLUSIONS: Tolvaptan increases urine volume and decreases urinary supersaturation in calcium stone formers. Further study is needed to determine if long-term use of V2 receptor antagonists results in fewer stone events.

Outcomes of patients with renal monoclonal immunoglobulin deposition disease.

Recent reports suggest that deep hematologic responses to chemotherapy are associated with improved renal outcomes in monoclonal immunoglobulin deposition disease (MIDD). Here we describe the long term outcomes and identify prognostic factors after first line treatment of the largest reported series of patients with MIDD. Between March 1992 and December 2014, 88 patients with MIDD were seen at Mayo Clinic, MN. Renal responses were defined using criteria used for light chain amyloidosis (AL) or those used by the IMWG. Sixty-one (69%) patients had a GFR < 30 mL/min/1.73 m2 and 16 (18%) were on renal replacement therapy at diagnosis. The interval between albuminuria or elevation in creatinine and MIDD diagnosis was 12 months suggesting a delay in diagnosis. Thirty-seven patients (42%) had at least a hematologic CR/VGPR. Fifty-three (60%) received an autologous stem cell transplant (ASCT) or proteasome inhibitor (PI)-based treatments. Patients receiving ASCT or PI-based therapies were more likely to achieve at least a hematologic CR/VGPR compared to those receiving other therapies: 66% vs 2%, p < 0.0001. Patients that achieved a hematologic CR were more likely to achieve a renal response (53% vs 24%, p = 0.001). Five year overall and renal survival for the entire cohort was 67% and 57%, respectively. In multivariate analyses, a baseline GFR < 20 mL/min/1.73 m2 and a renal response (using AL or IMWG criteria) were independently predictive of progression to dialysis. This study confirms that deep hematologic responses, best achieved with ASCT or PI-based therapies, are a prerequisite to achieving renal responses. Am. J. Hematol. 91:1123-1128, 2016. © 2016 Wiley Periodicals, Inc.

Hypomagnesemia linked to new-onset diabetes mellitus after kidney transplantation: A systematic review and meta-analysis.

BACKGROUND: New-onset diabetes after kidney transplantation (NODAT) is associated with both renal allograft failure and increased mortality. The objective of this meta-analysis was to evaluate the risk of NODAT in patients with hypomagnesemia. METHODS: A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through May, 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risk of NODAT in patients with hypomagnesemia were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Five cohort studies with 1699 patients were included in the analysis to assess the risk of NODAT in patients with hypomagnesemia. The pooled RR of NODAT in patients with hypomagnesemia was 1.25 (95% CI, 1.08-1.45). When meta-analysis was limited only to studies with the post-transplant hypomagnesemia, the pooled RR of NODAT was 1.22 (95% CI, 1.09-1.38). CONCLUSION: Our meta-analysis demonstrates a significant association between hypomagnesemia and NODAT in kidney transplant recipients. This finding suggests the need for a large randomized controlled trial-with very careful attention to assess the effects of normalizing Mg levels and the risk of NODAT.

The risk of kidney stones following bariatric surgery: a systematic review and meta-analysis.

BACKGROUND: With rising prevalence of morbid obesity, the number of bariatric surgeries performed each year has been increasing worldwide. The objective of this meta-analysis was to assess the risk of kidney stones following bariatric surgery. METHODS: A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through July 2015. Only studies reporting relative risks, odd ratios or hazard ratios (HRs) to compare risk of kidney stones in patients who underwent bariatric surgery versus no surgery were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Four studies (One randomized controlled trial and three cohort studies) with 11,348 patients were included in analysis to assess the risk of kidney stones following bariatric surgery. The pooled RR of kidney stones in patients undergoing bariatric surgery was 1.22 (95% CI, 0.63-2.35). The type of bariatric surgery subgroup analysis demonstrated an increased risk of kidney stones in patients following Roux-en-Y gastric bypass (RYGB) with the pooled RR of 1.73 (95% CI, 1.30-2.30) and a decreased risk of kidney stones in patients following restrictive procedures including laparoscopic banding or sleeve gastrectomy with the pooled RR of 0.37 (95% CI, 0.16-0.85). CONCLUSIONS: Our meta-analysis demonstrates an association between RYGB and increased risk of kidney stones. Restrictive bariatric surgery, on the other hand, may decrease kidney stone risk. Future study with long-term follow-up data is needed to confirm this potential benefit of restrictive bariatric surgery.

Preoperative renin-angiotensin system inhibitors use linked to reduced acute kidney injury: a systematic review and meta-analysis.

BACKGROUND: Previous trials of interventions to prevent acute kidney injury (AKI) have been unsuccessful and additional interventions are needed. Existing reviews of preoperative renin-angiotensin system (RAS) inhibitors have suggested harm. We included more recent studies and conducted this meta-analysis to evaluate the risk of postoperative AKI in patients who received preoperative RAS inhibitors. METHODS: A literature search was performed using MEDLINE, EMBASE and Cochrane Database of Systematic Reviews from inception through October, 2014. Studies that reported relative risks, odds ratios or hazard ratios comparing the AKI risk in patients who received preoperative RAS inhibitors versus those who did not were included. We performed the prespecified sensitivity analysis including only propensity score-based studies. Mortality risk was evaluated among the studies that reported AKI outcome. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Twenty-four studies (1 randomized controlled trial and 23 cohort studies) with 102 675 patients were included in the analysis to assess the risk of postoperative AKI and preoperative RAS inhibitors use. The pooled RR of AKI in patients receiving RAS inhibitors was 1.05 (95% CI: 0.92-1.20). The meta-analysis of the RCT and 11 studies with propensity score analysis demonstrated the pooled RR of AKI in patients receiving RAS inhibitors of 0.92 (95% CI: 0.85-0.99). Within the selected studies, preoperative RAS inhibitor therapy was not associated with a significant increase or decrease in mortality (RR: 0.93; 95% CI: 0.80-1.09). CONCLUSIONS: Our meta-analysis demonstrates an association between preoperative RAS inhibitor treatment and lower incidence of AKI.

Comparison of renal outcomes in off-pump versus on-pump coronary artery bypass grafting: A systematic review and meta-analysis of randomized controlled trials.

AIM: The objective of this meta-analysis was to compare the effects of off-pump and on-pump coronary artery bypass grafting (CABG) on acute kidney injury (AKI) and the need of dialysis after surgery. METHODS: Comprehensive literature searches for randomized controlled trials (RCTs) of CABG with on-pump and off-pump was performed using MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials Systematic Reviews and clinicaltrials.gov from inception through September 2014. Primary outcomes were the incidence of AKI and the need of dialysis. Mortality was assessed among the studies that reported renal outcomes. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Thirty-three RCTs with 17 322 patients were enrolled in our study. Patients in the off-pump CABG group had overall lower incidence of AKI (19.1%) compared with the on-pump CABG group (22.2%). There was a protective effect of off-pump CABG on the incidence of AKI compared with the on-pump CABG group (RR: 0.87; 95% CI: 0.77-0.98). However, there was no significant difference in the need for dialysis in the off-pump group compared with the on-pump group (RR: 0.84; 95% CI 0.63-1.13). Within the selected trials, post hoc analysis assessing the mortality outcome demonstrated a pooled RR of 0.97 (95% CI, 0.77-1.23) in off-pump versus on-pump CABGs. CONCLUSIONS: Our study demonstrates a beneficial effect of off-pump CABG on the incidence of AKI. However, our meta-analysis does not show benefits of the need of dialysis or survival among patients undergoing off-pump CABG.

Sugar and artificially sweetened soda consumption linked to hypertension: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: The risk of hypertension (HTN) in patients who regularly drink soda is controversial. The objective of this meta-analysis was to assess the associations between consumption of sugar and artificially sweetened soda and HTN. METHODS: A literature search was performed using MEDLINE, EMBASE and Cochrane Database of Systematic Reviews from inception through January 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risk of HTN in patients consuming a significant amount of either sugar or artificially sweetened soda versus those who did not consume soda were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Eight studies were included in our analysis to assess the association between consumption of sugar-sweetened soda and HTN. The pooled RR of HTN in patients consuming sugar-sweetened soda was 1.12 (95% CI, 1.03-1.23). Four studies were selected to assess the association between consumption of artificially sweetened soda and HTN. The pooled RR of HTN in patients consuming artificially sweetened soda was 1.15 (95% CI, 1.11-1.19). CONCLUSIONS: Our study demonstrates statistically significant associations between both sugar and artificially sweetened soda consumption and HTN. This finding may impact clinical management and primary prevention of HTN.

Admission hypomagnesemia linked to septic shock in patients with systemic inflammatory response syndrome.

BACKGROUND: The association between admission serum magnesium (Mg) levels and risk of developing septic shock in patients with systemic inflammatory response syndrome (SIRS) is limited. The aim of this study was to assess the risk of developing septic shock in hospitalized patients with SIRS with various admission Mg levels. METHODS: This is a single-center retrospective study conducted at a tertiary referral hospital. All hospitalized adult patients with SIRS at admission who had admission Mg available from January 2009 to December 2013 were analyzed in this study. Admission Mg was categorized based on its distribution into six groups (<1.5, 1.5-1.7, 1.7-1.9, 1.9-2.1, 2.1-2.3, and >2.3 mg/dL). The primary outcome was septic shock occurring after hospital admission. Logistic regression analysis was performed to obtain the odds ratio (OR) of septic shock of various admission Mg levels using Mg with lowest incidence of shock, 2.1-2.3 mg/dL as the reference group. RESULTS: Of 2589 patients with SIRS enrolled, septic shock occurred in 236 patients (9.1%). The lowest incidence of septic shock was when serum Mg was within 2.1-2.3 mg/dL. A reverse-checkmark curve emerged demonstrating higher incidences of septic shock associated with both hypoMg (<2.1) and hyperMg (>2.3). After adjusting for potential confounders, hypoMg (<1.5 mg/dL) was associated with an increased risk of developing septic shock with ORs of 1.86 (95% CI 1.07-3.27). CONCLUSION: Patients with SIRS and hypoMg (<1.5 mg/dL) at the time of admission had increased risk of developing septic shock during hospitalization.