Natalia Polanco

Spontaneous Remission of Nephrotic Syndrome in Idiopathic Membranous Nephropathy

Spontaneous remission is a well known characteristic of idiopathic membranous nephropathy, but contemporary studies describing predictors of remission and long-term outcomes are lacking. We conducted a retrospective, multicenter cohort study of 328 patients with nephrotic syndrome resulting from idiopathic membranous nephropathy that initially received conservative therapy. Spontaneous remission occurred in 104 (32%) patients: proteinuria progressively declined after diagnosis until remission of disease at 14.7 +/- 11.4 months. Although spontaneous remission was more frequent with lower levels of baseline proteinuria, it also frequently occurred in patients with massive proteinuria: 26% among those with baseline proteinuria 8 to 12 g/24 h and 22% among those with proteinuria >12 g/24 h. Baseline serum creatinine and proteinuria, treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, and a >50% decline of proteinuria from baseline during the first year of follow-up were significant independent predictors for spontaneous remission. Only six patients (5.7%) experienced a relapse of nephrotic syndrome. The incidence of death and ESRD were significantly lower among patients with spontaneous remission. In conclusion, spontaneous remission is common among patients with nephrotic syndrome resulting from membranous nephropathy and carries a favorable long-term outcome with a low incidence of relapse. A decrease in proteinuria >50% from baseline during the first year predicts spontaneous remission.

Efficacy and tolerability of interferon-free antiviral therapy in kidney transplant recipients with chronic hepatitis C

BACKGROUND & AIMS The development of direct-acting antiviral agents (DAAs) is a major step forward in the treatment of hepatitis C (HCV). The aims of the study were to evaluate the efficacy and tolerability of DAAs in kidney transplant (KT) recipients. METHODS Hepa-C is a Spanish registry of patients treated with DAAs in which clinical, virological and analytical data were prospectively included. We report on the data from 103 KT recipients who received DAAs. RESULTS The most commonly used DAAs combinations were sofosbuvir/ledipasvir (n=59, 57%) and sofosbuvir+daclatasvir (n=18, 17%). Ribavirin was used in 41% of patients. Sustained viral response after 12weeks (SVR12) rate was 98%. Grade 2 or 3 anemia appeared in 14 (33%) of patients receiving ribavirin and in 9 (15%) without (p=0.03). There were three episodes of acute humoral graft rejection. No patient discontinued therapy due to adverse events. Importantly, 57 (55%) patients required immunosuppression dose adjustment. Overall, there were no statistically significant differences in the mean level of serum creatinine, eGFR and proteinuria before and after treatment. Nonetheless, seventeen (16%) patients experienced renal dysfunction (increase in serum creatinine >25%) during antiviral therapy, of whom 65% were cirrhotic in comparison with only 29% cirrhotic patients who did not develop significant renal dysfunction (p=0.004). CONCLUSIONS Antiviral therapy with DAAs was highly efficacious and safe in KT recipients. Nevertheless, a non-negligible number of patients, most of them cirrhotic, developed mild allograft dysfunction and a significant proportion of patients required immunosuppression dose adjustment, warranting a close follow-up during therapy. LAY SUMMARY Infection by hepatitis C virus is often found in kidney transplant patients and its presence increases mortality and graft failure. We investigated the efficacy and safety of the new direct-acting hepatitis C antivirals in this population, in which previous information is scarce. Our data shows that, as occurs in the non-transplant setting, new anti-HCV antivirals are highly efficacious kidney transplant patients. Overall, this therapy is also quite safe, although worsening of renal function is observed in 16% of patients warranting a close follow-up observation of graft function during antiviral therapy.

Should asymptomatic bacteriuria be systematically treated in kidney transplant recipients? Results from a randomized controlled trial.

The indication for antimicrobial treatment of asymptomatic bacteriuria (AB) after kidney transplantation (KT) remains controversial. Between January 2011 and December 2013, 112 KT recipients that developed one episode or more of AB beyond the second month after transplantation were included in this open‐label trial. Participants were randomized (1:1 ratio) to the treatment group (systematic antimicrobial therapy for all episodes of AB occurring ≤24 mo after transplantation [53 patients]) or control group (no antimicrobial therapy [59 patients]). Systematic screening for AB was performed similarly in both groups. The primary outcome was the occurrence of acute pyelonephritis at 24‐mo follow‐up. Secondary outcomes included lower urinary tract infection, acute rejection, Clostridium difficile infection, colonization or infection by multidrug‐resistant bacteria, graft function and all‐cause mortality. There were no differences in the primary outcome in the intention‐to‐treat population (7.5% [4 of 53] in the treatment group vs. 8.4% [5 of 59] in the control group; odds ratio [OR] 0.88, 95% confidence interval [CI] 0.22–3.47) or the per‐protocol population (3.8% [1 of 26] in the treatment group vs. 8.0% [4 of 50] in the control group; OR 0.46, 95% CI 0.05–4.34). Moreover, we found no differences in any of the secondary outcomes. In conclusion, systematic screening and treatment of AB beyond the second month after transplantation provided no apparent benefit among KT recipients (NCT02373085).

Spontaneous remission of nephrotic syndrome in membranous nephropathy with chronic renal impairment

BACKGROUND Spontaneous remission (SR) of nephrotic syndrome, in the absence of immunosuppressive treatment, is relatively common among patients with idiopathic membranous nephropathy (IMN) and normal renal function. However, it has not been reported in patients with chronic renal impairment. METHODS All patients with IMN who had developed SR in the presence of chronic renal insufficiency were identified among the nephrology departments that belong to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). Their characteristics and outcome after SR were studied. RESULTS Eleven patients were identified. All of them showed renal insufficiency and nephrotic syndrome at the time of renal biopsy. Serum creatinine (Scr) continued to increase in the following months, reaching a peak value of 2.6 ± 1.5 mg/dL (range 1.7-6.5). Angiotensin converting enzyme inhibitors or spironolactone were prescribed in 10/11 patients at renal biopsy or shortly after it. Nephrotic proteinuria persisted during the first months of follow-up, but it started to spontaneously decrease 12 ± 7 months (2-30 months) after renal biopsy. Finally, complete (nine patients) or partial (two patients) remission of nephrotic syndrome was observed. Coinciding with proteinuria remission, renal function tended to improve. Nephrotic syndrome relapsed in two patients, accompanied by a rapid deterioration of renal function. In the remaining nine patients, remission persisted throughout a follow-up of 146 ± 64 months. Mean Scr at the last visit was 1.9 ± 0.9 mg/dL and proteinuria 0.2 g/24 h. CONCLUSION SR of nephrotic syndrome can also be observed in membranous nephropathy patients exhibiting chronic renal impairment.

Hypocomplementemia in Kidney Transplant Recipients: Impact on the Risk of Infectious Complications

The usefulness of monitoring of complement levels in predicting the occurrence of infection in kidney transplant (KT) recipients remains largely unknown. We prospectively assessed serum complement levels (C3 and C4) at baseline and at months 1 and 6 in 270 patients undergoing KT. Adjusted hazard ratios (aHRs) for infection in each posttransplant period were estimated by Cox regression. The prevalence of C3 hypocomplementemia progressively decreased from 21.5% at baseline to 11.6% at month 6 (p = 0.017), whereas the prevalence of C4 hypocomplementemia rose from 3.7% at baseline to 9.2% at month 1 (p = 0.004). Patients with C3 hypocomplementemia at month 1 had higher incidences of overall (p = 0.002), bacterial (p = 0.004) and fungal infection (p = 0.019) in the intermediate period (months 1–6). On multivariate analysis C3 hypocomplementemia at month 1 emerged as a risk factor for overall (aHR 1.911; p = 0.009) and bacterial infection (aHR 2.130; p = 0.014) during the intermediate period, whereas C3 hypocomplementemia at month 6 predicted the occurrence of bacterial infection (aHR 3.347; p = 0.039) in the late period (>6 month). A simple monitoring strategy of serum C3 levels predicts the risk of posttransplant infectious complications in KT recipients.

Impact of anti-HCV direct antiviral agents on graft function and immunosuppressive drug levels in kidney transplant recipients: a call to attention in the mid-term follow-up in a single-center cohort study

The medium‐term impact on graft function and immunosuppressive drug pharmacokinetics of direct antiviral agents (DAAs) among hepatitis C virus (HCV)‐infected kidney transplant (KT) recipients remain unclear. We compared pre‐ and post‐treatment 12‐month trajectories of estimated glomerular filtration rate (ΔeGFR) and 24‐h proteinuria (Δ24‐h proteinuria) in 49 recipients treated with DAAs (mostly sofosbuvir plus ledipasvir). Among evaluable patients, 66.7% and 100.0% had undetectable viral load by week 4 and end of therapy (EoT). The sustained virologic response rate at 12 weeks was 95.8%. Overall, 80.6% of patients receiving tacrolimus required dose escalation while on DAA‐based therapy (median increase of 66.7%) to maintain target levels. Tacrolimus levels resulted to be higher at 12 months compared to EoT (7.8 ± 2.1 vs. 6.7 ± 2.0 ng/ml; P‐value = 0.002). No changes in graft function during the course of therapy were observed. However, eGFR significantly decreased (P‐value <0.001) throughout the first 12 months after EoT. Median ΔeGFR and Δ24‐h over pre‐ and post‐treatment periods were 3.9% and −6.1% (P‐value = 0.002) and −5.3% and 26.2% (P‐value = 0.057). Caution should be exercised when adjusting immunosuppression in HCV‐infected KT recipients upon initiation of DAAs, followed by mid‐term monitoring of immunosuppressive drug levels and graft function.

Serum iron parameters in the early post-transplant period and infection risk in kidney transplant recipients

The impact of iron metabolism on the risk of infectious complications has been demonstrated in various immunosuppressed populations. However, no previous studies have assessed this potential association in kidney transplant (KT) recipients.

Pre-transplant dialysis modality does not influence short- or long-term outcome in kidney transplant recipients: analysis of paired kidneys from the same deceased donor.

Previous studies have reported contradictory results regarding the effect of pre‐transplant dialysis modality on the outcomes after kidney transplantation (KT). To minimize the confounding effect of donor‐related variables, we performed a donor‐matched retrospective comparison of 160 patients that received only one modality of pre‐transplant dialysis (peritoneal dialysis [PD] and hemodialysis [HD] in 80 patients each) and that subsequently underwent KT at our center between January 1990 and December 2007. Cox regression models were used to evaluate the association between pre‐transplant dialysis modality and primary study outcomes (death‐censored graft survival and patient survival). To control for imbalances in recipient‐related baseline characteristics, we performed additional adjustments for the propensity score (PS) for receiving pre‐transplant PD (versus HD). There were no significant differences according to pre‐transplant dialysis modality in death‐censored graft survival (PS‐adjusted hazard ratio [aHR]: 0.65; 95% confidence interval [95% CI]: 0.25–1.68) or patient survival (aHR: 0.58; 95% CI: 0.13–2.68). There were no differences in 10‐year graft function or in the incidence of post‐transplant complications either, except for a higher risk of lymphocele in patients undergoing PD (odds ratio: 4.31; 95% CI: 1.15–16.21). In conclusion, pre‐transplant dialysis modality in KT recipients does not impact short‐ or long‐term graft outcomes or patient survival.

Herpes zoster in kidney transplant recipients: protective effect of anti-cytomegalovirus prophylaxis and natural killer cell count. A single-center cohort study

Despite its impact on quality of life and potential for complications, specific risk and protective factors for herpes zoster (HZ) after kidney transplantation (KT) remain to be clarified. We included 444 patients undergoing KT between November 2008 and March 2013. Peripheral blood lymphocyte subpopulations were measured at baseline and months 1 and 6. The risk factors for early (first post‐transplant year) and late HZ (years 1–5) were separately assessed. We observed 35 episodes of post‐transplant HZ after a median follow‐up of 48.3 months (incidence rate: 0.057 per 1000 transplant‐days). Median interval from transplantation was 18.3 months. Six patients (17.1%) developed disseminated infection. Postherpetic neuralgia occurred in 10 cases (28.6%). The receipt of anti‐cytomegalovirus (CMV) prophylaxis with (val)ganciclovir decreased the risk of early HZ [adjusted hazard ratio (aHR): 0.08; 95% CI: 0.01–1.13; P‐value = 0.062], whereas the natural killer (NK) cell at month 6 was protective for the occurrence of late HZ [aHR (per 10‐cells/μl increase): 0.94; 95% CI: 0.88–1.00; P‐value = 0.054]. In conclusion, two easily ascertainable factors (whether the patient is receiving anti‐CMV prophylaxis and the NK cell count at month 6) might be potentially useful to tailor preventive strategies according to individual susceptibility to post‐transplant HZ.

Serum sCD30: A promising biomarker for predicting the risk of bacterial infection after kidney transplantation

The transmembrane glycoprotein CD30 contributes to regulate the balance between Th1 and Th2 responses. Previous studies have reported conflicting results on the utility of its soluble form (sCD30) to predict post‐transplant infection.