Stable Serum Creatinine Levels Research Articles

Tacrolimus Therapy Among Steroid-Resistant Nephrotic Syndrome Children: A Preliminary Study in West Java, Indonesia

Objective: To explore the outcomes of Tac therapy for Steroid-Resistant Nephrotic Syndrome (SRNS) and its implication in reducing the number of CKD events.Methods: An open, prospective, cohort study was conducted at a tertiary hospital in Bandung, West Java, Indonesia. Children (age 1–18 years old) with steroid and cyclophosphamide resistant nephrotic syndrome were enrolled in this study. Blood pressure, urinary protein, serum ureum, and creatinine levels were measured every month, Tac and soluble urokinase plasminogen activator receptor (supaR) levels were assessed at the 0, third, and sixth months.Results: Ten of fifteen subjects enrolled in this study got better within 3–6 months with a trend of decreasing suPAR level and proteinuria, as well as stable blood pressure and serum creatinine and ureum level. During treatment, no side effects of the subjects were found with the Tac level maintain safely.Conclusion: Tac is an effective and safe agent in treating SRNS, especially for those do not respond well to an alkylating agent.

Case report: Rare myeloid sarcoma development following renal transplantation with KRAS and DNMT3A gene mutations

BackgroundA high incidence of malignant tumors, such as post-transplant lymphoproliferative disorders (PTLD), Kaposi sarcoma, and renal cancer is common in solid organ and bone marrow transplant recipients. However, myeloid sarcoma (MS) after renal transplantation has rarely been reported and the diagnosis is challenging due to its low incidence.Case presentationHere, we report a rare case of a 49-year-old man who developed myeloid sarcoma (MS) in the transplanted kidney two years after renal transplantation. Next-generation sequencing (NGS) showed mutations of KRAS and DNMT3A genes in the MS, and no gene mutations in the bone marrow. He presented a normal karyotype of 46, XY. Following treatment with 6 cycles of systemic chemotherapy, the patient was in satisfactory condition with stable serum creatinine (sCr) levels at the 1-year follow-up. In addition, we performed a detailed review with emphasis on the clinical manifestations, and the diagnostic and therapeutic processes of another 7 patients who developed MS following renal transplantation.ConclusionsOur report illustrates the clinical utility of comprehensive genomic profiling in benefiting the diagnosis of MS, the selection of therapeutic strategy and the determination of whether MS is donor-derived.

Mechanical Anisotropy Assessment in Kidney Cortex Using ARFI Peak Displacement: Preclinical Validation and Pilot In Vivo Clinical Results in Kidney Allografts.

The kidney is an anisotropic organ, with higher elasticity along versus across nephrons. The degree of mechanical anisotropy in the kidney may be diagnostically relevant if properly exploited; however, if improperly controlled, anisotropy may confound stiffness measurements. The purpose of this study is to demonstrate the clinical feasibility of acoustic radiation force (ARF)-induced peak displacement (PD) measures for both exploiting and obviating mechanical anisotropy in the cortex of human kidney allografts, in vivo. Validation of the imaging methods is provided by preclinical studies in pig kidneys, in which ARF-induced PD values were significantly higher ( , Wilcoxon) when the transducer executing asymmetric ARF was oriented across versus along the nephrons. The ratio of these PD values obtained with the transducer oriented across versus along the nephrons strongly linearly correlated ( R2 = 0.95 ) to the ratio of shear moduli measured by shear wave elasticity imaging. On the contrary, when a symmetric ARF was implemented, no significant difference in PD was observed ( p > 0.01 ). Similar results were demonstrated in vivo in the kidney allografts of 14 patients. The symmetric ARF produced PD measures with no significant difference ( p > 0.01 ) between along versus across alignments, but the asymmetric ARF yielded PD ratios that remained constant over a six-month observation period post-transplantation, consistent with stable serum creatinine level and urine protein-to-creatinine ratio in the same patient population ( p > 0.01 ). The results of this pilot in vivo clinical study suggest the feasibility of 1) implementing symmetrical ARF to obviate mechanical anisotropy in the kidney cortex when anisotropy is a confounding factor and 2) implementing asymmetric ARF to exploit mechanical anisotropy when mechanical anisotropy is a potentially relevant biomarker.

Pre-Transplantation Biopsy-Proven Severe Tubular Injury Prolonged the Allograft Function Recovery After Deceased Kidney Transplantation

Background and Objectives The association between the pre-transplantation histologic acute tubular injury (ATI) and allograft function recovery after deceased kidney transplantation (KT) was unclear. This study aimed to evaluate the effect of ATI on the risk of DGF and the recovery time from DGF after deceased KT. Methods We retrospectively reviewed the pre-transplantation kidney biopsy from 141 kidney allograft recipients using deceased donor in the first affiliated hospital of Sun-Yat Sen University from Jan 2012 to June 2017. No organs from executed prisoners were used. ATI was assessed by two pathologists and the defrosted paraffin core biopsies were used for the assessment. Severe ATI is defined as extremely flattening of the tubular epithelia cells or the exposure of the basal membrane. DGF is defined as the need for dialysis within the first week post-transplant. DGF recovery time is defined as the time required to achieve stable serum creatinine level. The donor characteristics, the incidence of DGF and the recovery time from DGF were compared between severe ATI group and non-severe ATI group. Results There were 18 and 123 recipients in severe ATI group and non-severe ATI group respectively. Severe ATI was associated with increased donor terminal serum creatinine (median 260 vs 86.3 umol/L, p=0.001) and increased proportion of cardiac death (77.8% vs 30.1%, p<0.001). A significant increase in the risk of DGF was identified in severe ATI group compared with non-severe group (10/18, 55.6% vs 18/123, 14.6%, p<0.001; OR 7.32, 95% confidence interval 2.53-20.9, p<0.001). DGF recovery time was also prolonged in severe ATI group compared with non-severe group (49.6±10.5 vs 26.3±17.0, p<0.001). Conclusion Pre-transplantation kidney biopsy facilitated the evaluation of acute kidney injury and warm-ischemia-induced injury in the donor. Severe pre-transplantation histological ATI increased the risk of DGF and prolonged the recovery from DGF after deceased kidney transplantation.

Tongue Ulcers, Abdominal Pain, and Fever in a Kidney Transplant Recipient

Tongue Ulcers, Abdominal Pain, and Fever in a Kidney Transplant Recipient

Effectiveness and safety of conversion therapy with the combination of sirolimus with low dose cyclosporine in renal transplantation recipients: a five-year clinical observation

To assess the effectiveness and safety of the conversion therapy from traditional cyclosporine (CsA) triple immunosuppression therapy to sirolimus (SRL) combined with low dose CsA and prednisone (Pred) in renal transplantation recipients in a five-year follow-up period. A prospective, open-label non-randomized study was performed with 46 renal allograft recipients who visited Tongji Hospital regularly for follow-up visits between January 2007 and May 2011 and were taking CsA+ mycophenolate mofetil (MMF)+ Pred. Conversion therapy to SRL+ low dose CsA+ Pred was initiated after renal transplantation. The recipients were allocated to 2 groups according to their renal function and proteinuria before the conversion: active conversion group [n=27, serum creatinine (SCr) ≤ 140 μmol/L with no or minimal proteinuria] and passive conversion group [n=19, SCr>140 μmol/L with less than moderate proteinuria]. After conversion, dosages of SRL and CsA were adjusted for trough levels of 5-7 μg/L and 20-60 μg/L, respectively. SCr and urine protein were compared before and after the conversion in five-year follow-up. Incidence of acute rejection, renal graft survival and SRL-related adverse effects of the immunosuppressive regimen were also observed. After conversion, an average 63% dose reduction of CsA was achieved in all the patients. In the active conversion group, the mean SCr level was (110±19) μmol/L at the time of conversion. Eight patients in this group withdrew from the study during the follow-up period for the following reasons: arthralgia (1 case), deteriorated proteinuria (2 cases), chronic diarrhea (2 cases), mild or suspicious acute rejection (2 cases), and recurrent fever (1 case). The rest patients (19/27) with a mean follow-up time of 5 years had a stable SCr level [(103±12) μmol/L] and a 100% 5-year graft survival. In the passive conversion group, the mean SCr level was (205±45) μmol/L at the time of conversion. There were 4 patients quitting the study, 2 for deteriorated proteinuria and 2 for lost to follow-up. Chronic allograft failure developed in 10 patients in this group 1-50 months after conversion, while the remaining 5 patients had a stable SCr during the 5-year follow-up period [(218 ±46) μmol/L before conversion vs (205±73) μmol/L 5 years after conversion]. The overall 5-year graft survival after the conversion therapy in the passive conversion group was 33.3%, significantly lower than that of the active conversion group (P<0.001). Acute rejection was observed in 2 cases in the active conversion group, while not observed in the passive conversion group. None of the patients developed leukopenia, thrombocytopenia, oral ulcer, or pneumonia in the follow-up. The combination therapy of SRL and low dose of CsA is overall a safe and effective maintenance immunosuppressive regimen, but it is important to initiate at an appropriate stage. More favourable long-term benefits may be obtained from the conversion therapy in patients with normal or only slightly impaired renal graft function. It may offer an option of individualized immunosuppressive therapy after renal transplantation.

Risk of Acute Kidney Injury, Dialysis, and Mortality in Patients With Chronic Kidney Disease After Intravenous Contrast Material Exposure

ObjectiveTo examine the effect of intravenous iodinated contrast material administration on the subsequent development of acute kidney injury (AKI), emergent dialysis, and short-term mortality using a propensity score–adjusted analysis of computed tomographic scan recipients with chronic kidney disease (CKD). Patients and MethodsIn this institutional review board–approved retrospective study, all patients with CKD who received a contrast-enhanced (contrast group) or unenhanced (noncontrast group) computed tomographic scan from January 1, 2000, to August 1, 2013 were identified. Patients were subdivided into CKD stage III (baseline estimated glomerular filtration rate, 30-59 mL/min per 1.73 m2) and CKD stage IV-V (baseline estimated glomerular filtration rate, <30 mL/min per 1.73 m2) subgroups and separately underwent propensity score generation, stratification, and 1:1 matching. Rates of AKI, 30-day emergent dialysis, and mortality were compared between contrast and noncontrast groups. Sensitivity analyses examining only patients with stable prescan serum creatinine levels and incorporating intravenous fluid administration at the time of the CT scan into the model were also performed. ResultsA total of 6902 patients (4496 CKD stage III, matched: 1220 contrast and 1220 noncontrast; 2086 CKD stage IV-V, matched: 491 contrast and 491 noncontrast) were included in the study. After propensity score adjustment, rates of AKI, emergent dialysis, and mortality were not significantly higher in the contrast group than in the noncontrast group in either CKD subgroup (CKD stage III: OR, 0.65-1.00; P<.001-.99 and CKD stage IV-V: OR, 0.93-2.33; P=.22-.99). Both sensitivity analyses revealed similar results. ConclusionIntravenous contrast material administration was not associated with an increased risk of AKI, emergent dialysis, and short-term mortality in a cohort of patients with diminished renal function.

Oral galactose in children with focal and segmental glomerulosclerosis: a novel adjunct therapy.

Oral galactose in children with focal and segmental glomerulosclerosis: a novel adjunct therapy.

Ascorbic Acid for the Prevention of Contrast‐Induced Nephropathy After Coronary Angiography in Patients With Chronic Renal Impairment: A Randomized Controlled Trial

To determine the incidence of contrast-induced nephropathy (CIN) and to assess the effectiveness of ascorbic acid in the prevention of CIN after coronary angiography in patients with chronic renal impairment. CIN is the third most common cause of hospital-acquired renal failure. It is well documented that periprocedural hydration is effective in the prevention of CIN. Little data exist on the effectiveness of ascorbic acid, a vitamin with antioxidative action. Patients with stable serum creatinine level >107 μmol/L (n = 81) undergoing coronary angiography were randomized to receive either ascorbic acid (N = 40) or placebo (N = 41) before the procedure. All patients received intravenous volume expansion with normal saline before the procedure. CIN was defined as an increase of serum creatinine level >25% from baseline measured 3 to 4 days after the procedure. CIN occurred totally in 5/81 patients (6.2%); in two patients (3%) in the ascorbic acid group and in three patients (7.3%) in the placebo group (P = 0.512). Postprocedural worsening of renal function (postprocedural increase of serum creatinine level) was present in 10/81 patients (12.3%) in the ascorbic acid group and in 19/81 patients (23.4%) in the placebo group (P = 0.038). No patient required dialysis treatment. We found no statistically significant impact of ascorbic acid on the incidence of CIN in patients with chronic renal impairment undergoing coronary arteriography or angioplasty. Ascorbic acid may still have some protective role in CIN reflected in lower incidence of worsening of renal function in the treated group.

Cyclosporine-Associated Nephrotoxicity

Cyclosporine (CsA) has revolutionized transplant medicine and is currently one of the most important immunosuppressive agents for a wide range of organ transplantations and of autoimmune and inflammatory diseases, such as rheumatoid arthritis, uveitis, psoriasis, and atopic dermatitis. Renal impairment represents the main limitation to CsA long-term continuous therapy. However, it has been shown that nephrotoxicity is associated with longer treatment duration, larger cumulative doses and higher daily dose of CsA. With low dose regimens (<5 mg/kg/day), stable serum creatinine levels have been observed up to 15-20 years after kidney transplantation. Intermittent therapy may offer a good therapeutic strategy to limit long-term renal dysfunction, given the fact that renal structural changes are dose- and time-dependent. The best predictor of permanent renal damage is a persistent increase in serum creatinine level one month after treatment withdrawal. In patients with autoimmune diseases, the percentage increase in serum creatinine above baseline value during CsA therapy has been shown to predict CsA-induced nephropathy. Before CsA therapy initiation, patients should undergo a thorough baseline evaluation including laboratory assessments, in particular electrolytes, serum creatinine, and urea levels. Furthermore, patients should be evaluated for factors that might increase the risk of nephrotoxicity, such as obesity, older age, hypertension, concomitant use of nephrotoxic drugs, and pre-existing renal conditions. In the present paper, CsA-induced nephropathy will be reviewed in terms of pathophysiology, pathologic and clinical findings, and strategies for prevention and management.

MESNA (sodium 2-mercaptoethanesulfonate) for prevention of contrast medium-induced nephrotoxicity – controlled trial

The purpose of this study was to examine the efficacy of sodium 2-mercaptoethanesulfonate (MESNA), a reactive oxygen scavenger, in at-risk patients given radiographic contrast agents. Contrast-induced nephropathy (CIN) is a common complication of radiographic procedures; reactive oxygen species (ROS) could play a key role. We conducted a randomized, double-blinded, placebo-controlled trial in 100 patients with stable serum creatinine levels ≥ 150 µmol/l. They received an infusion of either 1,600 mg of MESNA (n = 51) or placebo (n = 49) plus 0.9% saline prior to and after contrast administration. CIN was defined as a ≥ 25% increase in serum creatinine after 48 h compared to baseline. CIN occurred in 7 patients in the placebo group and none in the MESNA group (p = 0.005). The adjusted odds ratio for CIN was 0.17 (95% confidence interval 0.03 - 0.80, p = 0.026) in the MESNA group compared to the placebo group. Cystatin C concentrations decreased slightly in the MESNA group but increased in the control group (p < 0.05). MESNA plus volume expansion before and during contrast exposure was effective in this single-center study for preventing CIN compared to volume expansion alone.

Short-term Outcomes of Induction Therapy With Tacrolimus Versus Cyclophosphamide for Active Lupus Nephritis: A Multicenter Randomized Clinical Trial

Intravenous cyclophosphamide with prednisone is an effective treatment for lupus nephritis, but with significant toxicities. We compared the efficacy and safety of tacrolimus versus intravenous cyclophosphamide as induction therapy. Multicenter noninferiority randomized controlled trial. 81 patients with biopsy-proven lupus nephritis from 9 nephrology centers in China from 2006-2008. Prednisone and either tacrolimus (n = 42) or intravenous cyclophosphamide (n = 39) for 6 months. Tacrolimus was started at 0.05 mg/kg/d and titrated to achieve a trough blood concentration of 5-10 ng/mL. Intravenous cyclophosphamide was initiated at 750 mg/m² of body surface area, then adjusted to 500-1,000 mg/m² every 4 weeks for a total of 6 pulse treatments. The primary outcome was complete remission (proteinuria with protein excretion <0.3 g/24 h, serum albumin ≥3.5 g/dL, normal urinary sediment, and normal or stable serum creatinine level) at 6 months. Response (complete or partial remission), clinical parameters, and adverse effects were secondary end points. After the 6-month induction therapy, the tacrolimus group achieved higher cumulative probabilities of complete remission and response (52.4% vs 38.5% and 90.5% vs 82.1%, respectively) than the intravenous cyclophosphamide group, but differences were not statistically significant (log-rank test, P = 0.2 and P = 0.7, respectively). Proteinuria [corrected] was significantly decreased in tacrolimus- versus intravenous cyclophosphamide-treated patients after the first month of treatment, even with adjustment for baseline proteinuria (protein excretion, 1.76 vs 2.40 g/d; P = 0.02 for the log-transformed analysis). [corrected] After treatment, serum creatinine levels and estimated glomerular filtration rates were not significantly different between treatment groups. Adverse effects, such as leukopenia and gastrointestinal symptoms, were less frequent in the tacrolimus group. Nonblinded, small sample size, and short duration of follow-up. In conjunction with prednisone, induction therapy with tacrolimus is at least as efficacious as intravenous cyclophosphamide and prednisone in producing complete remission of lupus nephritis and has a more favorable safety profile.

Gastrointestinal symptoms impair quality of life in Italian renal transplant recipients but are under-recognized by physicians

We assessed patient- and physician-reported prevalence of gastrointestinal symptoms and their impact on quality of life (QOL) in Italian renal transplant recipients with stable graft function. Patients ≥18years with a renal allograft functioning for ≥6months and stable serum creatinine levels of <2.5mg/dl were enrolled. Physicians and patients completed an Italian translation of the Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI) questionnaires. The average time since transplantation (n=1130) was 5.9years. Forty-two immunosuppressant drug regimens were reported. The top three regimens (cyclosporine/mycophenolate mofetil/steroids; tacrolimus/mycophenolate mofetil/steroids; cyclosporine/steroids) accounted for approximately 40% of patients. In the physician interview, 39.2% of patients had ≥1 gastrointestinal symptom vs. 88.3% of patients in the self-administered questionnaire. The prevalence of GSRS symptoms was similar for each of the most frequently prescribed immunosuppressant drug regimens. GIQLI total score was significantly poorer in patients with versus those without gastrointestinal symptoms (121.8±17.6 vs. 138.4±3.7; P<0.0001), and there was a strong inverse correlation between GIQLI and patient-reported GSRS scores (Pearson's correlation coefficient -0.816; P<0.0001). Gastrointestinal symptoms are frequent in renal transplant patients, are under-evaluated by physicians and may adversely impact on patient QOL.

Catastrophic antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease with clinical manifestations of arterial and venous thrombosis, concomitant fetal loss and the presence of antiphospholipid antibodies (APLA). This report focuses on the challenges of optimal treatment involving plasma exchange and intravenous human immunoglobulin infusions that is administered in patients with catastrophic APS (CAPS). CAPS is a rare variant of APS defined as acute failure of at least three tissues, organs or systems caused predominantly by small vessel thrombosis confirmed by histopathologic evidence. CAPS develops rapidly and leads to death in 50% of cases. We present the case of a 39-year-old male patient with APS with worsening renal function. Positive lupus anticoagulant, markedly high concentrations of anticardiolipin and anti-beta 2-glikoprotein I antibodies have been observed. According to the criteria introduced by Asherson, a catastrophic form of APS was diagnosed and the patient had been treated with low-molecular-weight heparin, glucocorticosteroids, and plasmapheresis. In order to maintain clinical improvement, the patient was given human immunoglobulins i.v. (1 g/kg body weight). After the procedure, gradual clinical improvement was observed and renal function remained stable (serum creatinine level of 1.5 mg/dl).

Association of cytokine polymorphisms with subclinical progressive chronic allograft nephropathy in Japanese renal transplant recipients: Preliminary study

The present study calculated the risk of developing subclinical progressive chronic/sclerosing allograft nephropathy (CAN) under tacrolimus-based immunosuppression according to genetic polymorphisms of cytokines and growth factors, and clinical events including delayed graft function (DGF), acute rejection (AR) and cytomegalovirus (CMV) infection. The subjects were 50 recipients with stable graft function more than one year after renal transplantation. The criteria for subclinical progressive CAN were CAN grade 2 or 3 changes on Banff classification and stable serum creatinine (SCr) levels. Ten genetic polymorphisms were assessed. Eleven patients (22.0%) developed progressive CAN. The mean ages and SCr levels of recipients with and without progressive CAN were 41.2 and 47.1 years, and 1.46 and 1.22 mg/dL, respectively. There were no significant differences in donor age, number of HLA mismatches, DGF or CMV infection. Although the rate of AR episode seemed to be greater in patients with subclinical progressive CAN, the difference did not reach significance (P = 0.093). The frequencies of the interleukin (IL)-2 T-330G TT genotype (P = 0.046) and IL-4 C-590T C allele (P = 0.092) were higher in patients with progressive CAN. In univariate analysis, the presence of IL-2 T-330G TT (OR 4.57, P = 0.044) was associated with CAN development. The presence of IL-2 T-330G TT genotype may be a risk factor for CAN. Further studies with a large number of subjects and analyses of many cytokine polymorphisms would contribute to the ability to make prognostic determinations or tailor immunomodulatory regimens after renal transplantation.

Potential Renal Protective Benefits of Intra-Operative BNP Infusion During Cardiac Transplantation

Background Recombinant BNP (nesiritide) is known to reduce endothelin levels, cause afferent arteriole vasodilation, and increase natriuresis and diuresis. We hypothesized that intraoperative infusion of BNP may benefit renal function in cardiac transplant patients. Methods From June 2003 to September 2005, 22 consecutive heart transplant patients received BNP at a dose of 0.01 μg/kg/min before initiation of cardiopulmonary bypass (group A). BNP infusion was continued for a mean of 3.3 ± 1.9 days. Hemodynamics, urine output, and serum creatinine levels were prospectively collected and compared with 22 consecutive patients who underwent heart transplantation between May 2002 and June 2003 following the identical transplant protocol, but without BNP infusion (group B). Results At 24 hours postoperatively, mean blood pressure was comparable between groups (87 ± 11 mm Hg vs 89 ± 17 mm Hg, P = .7), but pulmonary artery pressure (18 ± 5 mm Hg vs 24 ± 5 mm Hg, P = .001) and central venous pressure (12 ± 5 mm Hg vs 16 ± 4 mm Hg, P = .01) were lower with BNP infusion, whereas cardiac index was augmented (2.8 ± 0.5 vs 2.4 ± 0.6, P = .03). Requirement of low-dose inotropic and vasopressor support was equally distributed between groups ( P ≥ .72). Postoperative urine output for the initial 24 hours was higher in group A (84 ± 15 vs 55 ± 36 mL/h, P = .01). None of the patients with BNP infusion required additional diuretics or renal replacement therapy during the first week after transplantation. Mean postoperative serum creatinine levels as compared with preoperative values remained unchanged within group A ( P = .12), but increased significantly in group B ( P < .001). Conclusions Intraoperative BNP infusion in heart transplant recipients was associated with favorable postoperative hemodynamics, significantly improved urine output, and stable serum creatinine levels. A prospective, randomized, multicenter trial is warranted to evaluate the potential renal protective benefits of intraoperative BNP infusion in this patient population.

Sarcoid relapse with isolated kidney involvement

A 70-year-old Caucasian male presented with history of systemic symptoms lasting since several weeks including malaise, anorexia, weight loss, and low-grade fever. He had no other significant symptoms or clinical findings, physical examination was unrevealing, and vital parameters were normal. When the patient was 45 yeas old, a diagnosis of pulmonary sarcoid was made upon results of radiologic imaging tests, gallium-67 scanning, and the histological demonstration of non-caseating granulomas at a transbronchial lung biopsy. At that time, all other known causes of granulomatous lung inflammation were ruled out and complete recovery was achieved after 6 months of steroid treatment at tapering doses. Afterwards, he had several episodes of recurrent right flank pain, which were managed conservatively; 10 months before admission lithotripsy was performed and calcium oxalate urinary stones recovered. At that time, serum creatinine was 2.1 mg/dl (normal range 0.5-1.2 mg/dl), urea was 72 mg/dl (normal range 10-50 mg/dl), and calcium was 12.4 mg/dl (normal range 8.1-10.4 mg/dl). Follow-up laboratory results until 1 month before presentation revealed persistent mild hypercalcaemia, with calcium blood levels ranging from 10.6 to 11.2 mg/dl, and stable serum creatinine and urea levels; the other variables remained within normal ranges on each occasion. There was no personal and family history of hypertension or any other cardiovascular, metabolic or systemic disorders, and the patient denied alcohol use, toxic habits, or taking any other medications, including over-the-counter medications, or herbal remedies. On admission, laboratory analyses showed renal impairment with a glomerular filtration rate of 14 ml/min; serum creatinine was 4.1 mg/dl, urea was 106 mg/dl, and calcium was 14.4 mg/dl. Electrolytes, a complete blood count, uric acid, cholesterol, triglycerides, protein, amylase and lipase, liver function tests, intact parathyroid hormone, and the coagulation profile were all normal; the erythrocyte sedimentation rate was 50 mm/h. Urinalysis showed a pH of 6.5, a specific gravity of 1012, and the urine tested positive for occult blood; there were between 5 and 10 red cells and calcium oxalate crystals per high-power field with no white cells, casts, or bacteria. Cultures grew no pathogens and the 24h urinary protein excretion was < 500 mg. Complement was normal and search for autoantibodies, including antinuclear, antiphospholipid, and antineutrophil cytoplasmic antibodies, rheumatoid factor, cryoglobulins, and lupus anticoagulant was also negative; blood levels of angiotensin-converting enzyme (ACE) were not measured at this time. An electrocardiogram did not show any abnormalities and a chest

Urine Cytokines Profile in Renal Transplant Patients with Asymptomatic Bacteriuria

The role of asymptomatic bacteriuria in kidney transplant recipients is unknown. There is no clear evidence of its effect on transplanted kidney. We studied urine cytokines profile among kidney transplant recipients with bacteriuria found in screening examination. Urine cultures were collected in 269 patients with stable graft function and serum creatinine level <2 mg/dl, during their routine visits. Interleukin (IL)-6 and IL-8 levels were measured in urine samples from patients with asymptomatic bacteriuria, symptomatic urinary tract infection and patients without bacteriuria (control group). Changes in serum creatinine level in patients with asymptomatic bacteriuria and in the control group were observed during 12 months follow up. Urinary tract infection (UTI) was diagnosed in five patients and asymptomatic bacteriuria in 22 patients. Urine IL-6 level was significantly higher in symptomatic UTI group (median 15.71 pg/mg) but there were no differences between group of patients with asymptomatic bacteriuria (3.92 pg/mg) and control group (2.54 pg/mg). Urine IL-8 level was higher in symptomatic UTI group (median 146.8 pg/mg) and was also significantly higher in asymptomatic bacteriuria group (33.49 pg/mg) in comparison to control group (2.97 pg/mg; P=0.0002). During 1-year follow up, incidence of UTI was higher in the asymptomatic bacteriuria group than in the control group but graft function was not different in both groups. Elevated urine IL-8 level in kidney transplant patients with asymptomatic bacteriuria may reflect impaired immune response to bacterial infection and occult inflammatory process in urinary tract.

Prevention of Contrast-Induced Nephropathy With Sodium Bicarbonate

Contrast-induced nephropathy remains a common complication of radiographic procedures. Pretreatment with sodium bicarbonate is more protective than sodium chloride in animal models of acute ischemic renal failure. Acute renal failure from both ischemia and contrast are postulated to occur from free-radical injury. However, no studies in humans or animals have evaluated the efficacy of sodium bicarbonate for prophylaxis against contrast-induced nephropathy. To examine the efficacy of sodium bicarbonate compared with sodium chloride for preventive hydration before and after radiographic contrast. A prospective, single-center, randomized trial conducted from September 16, 2002, to June 17, 2003, of 119 patients with stable serum creatinine levels of at least 1.1 mg/dL (> or =97.2 micromol/L) who were randomized to receive a 154-mEq/L infusion of either sodium chloride (n = 59) or sodium bicarbonate (n = 60) before and after iopamidol administration (370 mg iodine/mL). Serum creatinine levels were measured at baseline and 1 and 2 days after contrast. Patients received 154 mEq/L of either sodium chloride or sodium bicarbonate, as a bolus of 3 mL/kg per hour for 1 hour before iopamidol contrast, followed by an infusion of 1 mL/kg per hour for 6 hours after the procedure. Contrast-induced nephropathy, defined as an increase of 25% or more in serum creatinine within 2 days of contrast. There were no significant group differences in age, sex, incidence of diabetes mellitus, ethnicity, or contrast volume. Baseline serum creatinine was slightly higher but not statistically different in patients receiving sodium bicarbonate treatment (mean [SD], 1.71 [0.42] mg/dL [151.2 [37.1] micromol/L] for sodium chloride and 1.89 [0.69] mg/dL [167.1 [61.0] micromol/L] for sodium bicarbonate; P =.09). The primary end point of contrast-induced nephropathy occurred in 8 patients (13.6%) infused with sodium chloride but in only 1 (1.7%) of those receiving sodium bicarbonate (mean difference, 11.9%; 95% confidence interval [CI], 2.6%-21.2%; P =.02). A follow-up registry of 191 consecutive patients receiving prophylactic sodium bicarbonate and meeting the same inclusion criteria as the study resulted in 3 cases of contrast-induced nephropathy (1.6%; 95% CI, 0%-3.4%). Hydration with sodium bicarbonate before contrast exposure is more effective than hydration with sodium chloride for prophylaxis of contrast-induced renal failure.

Treatment of idiopathic nephrosis by immunophillin modulation.

Until 1985, glucocorticoids and cytotoxic drugs were the only treatments available for idiopathic nephrotic syndrome (nephrosis), that is, minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). Trials of cyclosporine (CsA) treatment of nephrosis, the rationale of which was based on pathophysiologic considerations, have shown that this immunophillin modulator is effective in inducing and maintaining remission in patients suffering from idiopathic nephrotic syndrome. It appears that the best results, in the order of 80% remission rate, are obtained in steroid-sensitive cases, essentially MCD, and that in steroid-resistant FSGS the drug obtains remission in no more than 20% of the cases. Addition of glucocorticoids increases the success rate to approximately 30% of cases. Renal toxicity is proportional to previous impairment of renal function, primary renal disease (FSGS vs MCD) dosage >5.5 mg/kg/day and duration of treatment. The better bioavailability of the new formulation of CsA (Neoral), implies that the former dosage recommendations be reconsidered for distinctly lower figures. Repeat renal biopsy after 1 year of continuous CsA treatment is advisable, as stable serum creatinine levels may be falsely reassuring. CsA dependency is the rule during the first year of treatment. However, in some 25% of cases stable remission may be maintained after slow tapering off following 3-4 years of treatment. Other immunophillin modulators have been tried in the treatment of idiopathic nephrotic syndrome. Despite few preliminary reports indicating some success of tacrolimus the effects of this drug do not seem convincingly superior to CsA in terms of remission rate, toxicity and dependency. Rapamycin has not been tried in the treatment of nephrosis. Anecdotal cases of de novo FSGS induced by rapamycin in transplanted patients might indicate that this drug is in fact contraindicated in the treatment of nephrosis.