One of the biggest challenges nephrologists face is to predict complex clinical pathways of kidney disease progression that do not follow a steady linear decline. This unpredictability often becomes ...a barrier to timely shared decision making between patients and physicians and could lead to adverse patient outcomes. By using numerous analytic approaches to characterize the longitudinal changes in kidney function, emerging evidence has disclosed the heterogeneous trajectories of kidney disease progression, particularly in late-stage chronic kidney disease (CKD) nearing end-stage renal disease (ESRD), and showed their independent associations with various clinical outcomes. These findings, in turn, have reinforced the importance of incorporating individual kidney disease trajectories into the clinical management of patients with late-stage CKD, which may help clarify the optimal timing of preparatory interventions, such as vascular access planning and transplant referral, and deliver better care with potential downstream benefits, such as a lower incidence of ESRD or a more seamless transition to ESRD. In this article, we review the current evidence on trajectories of kidney disease progression, particularly among patients with late-stage CKD progressing to ESRD, and discuss their implications for clinical management.
Background Mortality is extremely high immediately after the transition to dialysis therapy, but the association of blood pressure (BP) before dialysis therapy initiation with mortality after ...dialysis therapy initiation remains unknown. Study Design Observational study. Setting & Participants 17,729 US veterans transitioning to dialysis therapy in October 2007 to September 2011, with a median follow-up of 2.0 years. Predictor Systolic (SBP) and diastolic BP (DBP) averaged over the last 1-year predialysis transition period as 6 (<120 to ≥160 mm Hg in 10−mm Hg increments) and 5 (<60 to ≥90 mm Hg in 10−mm Hg increments) categories, respectively, and as continuous measures. Outcomes & Measurements Postdialysis all-cause mortality, assessed over different follow-up periods (ie, <3, 3-<6, 6-<12, and ≥12 months after dialysis therapy initiation) using Cox regressions adjusted for demographics, comorbid conditions, medications, cardiovascular medication adherence, body mass index, estimated glomerular filtration rate, and type of vascular access. Results Mean predialysis SBP and DBP were 141.2 ± 16.1 (SD) and 73.7 ± 10.6 mm Hg, respectively. There was a reverse J-shaped association of SBP with all-cause mortality, with significantly higher mortality seen with SBP < 140 mm Hg. Mortality risks associated with lower SBP were greatest in the first 3 months after dialysis therapy initiation, with multivariable-adjusted HRs of 2.40 (95% CI, 1.96-2.93), 1.99 (95% CI, 1.66-2.40), 1.35 (95% CI, 1.13-1.62), 0.98 (95% CI, 0.78-1.22), and 0.76 (95% CI, 0.57-1.00) for SBP <120, 120 to <130, 130 to <140, 150 to <160, and ≥160 (vs 140-<150) mm Hg, respectively. No consistent association was observed between predialysis DBP and postdialysis mortality. Limitations Results cannot be inferred to show causality and may not be generalizable to women or the general US population. Conclusions Lower predialysis SBP is associated with higher all-cause mortality in the immediate postdialysis period. Predialysis DBP showed no consistent association with postdialysis mortality. Further studies are needed to clarify ideal predialysis SBP levels among incident dialysis patients as a potential means to improve the excessively high early dialysis mortality.
Background Medication nonadherence is a known risk factor for adverse outcomes in the general population. However, little is known about the association of predialysis medication adherence among ...patients with advanced chronic kidney disease and mortality following their transition to dialysis. Study Design Observational study. Setting & Participants 32,348 US veterans who transitioned to dialysis during 2007 to 2011. Predictors Adherence to treatment with cardiovascular drugs, ascertained from pharmacy database records using proportion of days covered (PDC) and persistence during the predialysis year. Outcomes Post–dialysis therapy initiation all-cause and cardiovascular mortality, using Cox models with adjustment for confounders. Results Mean age of the cohort was 72 ± 11 (SD) years; 96% were men, 74% were white, 23% were African American, and 69% had diabetes. During a median follow-up of 23 (IQR, 9-36) months, 18,608 patients died. Among patients with PDC > 80%, there were 14,006 deaths (mortality rate, 283 95% CI, 278-288/1,000 patient-years); among patients with PDC > 60% to 80%, there were 3,882 deaths (mortality rate, 294 95% CI, 285-304/1,000 patient-years); among patients with PDC ≤ 60%, there were 720 deaths (mortality rate, 291 95% CI, 271-313/1,000 patient-years). Compared with patients with PDC > 80%, the adjusted HR for post–dialysis therapy initiation all-cause mortality for patients with PDC > 60% to 80% was 1.12 (95% CI, 1.08-1.16), and for patients with PDC ≤ 60% was 1.21 (95% CI, 1.11-1.30). In addition, compared with patients showing medication persistence, adjusted HR risk for post–dialysis therapy initiation all-cause mortality for patients with nonpersistence was 1.11 (95% CI, 1.05-1.16). A similar trend was detected for cardiovascular mortality and in subgroup analyses. Limitations Large number of missing values; results may not be generalizable to women or the general US population. Conclusions Predialysis cardiovascular medication nonadherence is an independent risk factor for postdialysis mortality in patients with advanced chronic kidney disease transitioning to dialysis therapy. Further studies are needed to assess whether interventions targeting adherence improve survival after dialysis therapy initiation.
To investigate the association of estimated glomerular filtration rate (eGFR) slopes before dialysis initiation with cause-specific mortality after dialysis initiation.
In this retrospective cohort ...study of 18,874 US veterans who had transitioned to dialysis from October 1, 2007, through September 30, 2011, we examined the association of pre-end-stage renal disease (ESRD) eGFR slopes with all-cause, cardiovascular, and infection-related mortality during the post-ESRD period over a median follow-up of 2.0 years (interquartile range, 1.1-3.2 years). Associations were examined using Cox models with adjustment for potential confounders.
Before the 18,874 patients transitioned to dialysis, 4485 (23.8%), 5633 (29.8%), and 7942 (42.1%) experienced fast, moderate, and slow eGFR decline, respectively, and 814 (4.3%) had increasing eGFR (defined as eGFR slopes of less than -10, -10 to less than -5, -5 to <0, and ≥0 mL/min per 1.73 m(2) per year). During the study period, a total of 9744 all-cause, 2702 cardiovascular, and 604 infection-related deaths were observed. Compared with patients with slow eGFR decline, those with moderate and fast eGFR decline had a higher risk of all-cause mortality (adjusted hazard ratio HR, 1.06; 95% CI, 1.00-1.11; and HR, 1.11; 95% CI, 1.04-1.18, respectively) and cardiovascular mortality (HR, 1.11; 95% CI, 1.01-1.23 and HR, 1.13; 95% CI, 1.00-1.27, respectively). In contrast, increasing eGFR was only associated with higher infection-related mortality (HR, 1.49; 95% CI, 1.03-2.17).
Rapid eGFR decline is associated with higher all-cause and cardiovascular mortality, and increasing eGFR is associated with higher infection-related mortality among incident dialysis cases.
Summary Allogeneic hematopoietic stem cell transplantation (HSCT)-related membranous glomerulonephritis (MGN) is poorly understood. A total of 830 patients who underwent HSCT at Toranomon Hospital ...from 2000 to 2012 were evaluated retrospectively, including 621 patients receiving umbilical cord blood transplantation (UCBT) and 208 patients receiving unrelated bone marrow transplantation (BMT). MGN was diagnosed in 5 patients after UCBT (vs. none after BMT), and occurred concomitantly with chronic graft-versus-host-disease after cessation of immunosuppression. LM did not show any definite spikes or bubbling of the glomerular basement membrane (GBM) in all 5 patients. In 1 patient (case 5), endocapillary proliferative lesions with fibrin-like deposits were noted in addition to MGN findings. IF demonstrated granular deposits of IgG (IgG1 and IgG4) along the GBM with negativity for C3, C4, and C1q in 4 patients (cases 1-4), while case 5 showed positivity for IgG (IgG1, IgG2, IgG3, and IgG4) as well as for C3, C4, and C1q. EM revealed electron-dense deposits (EDD) in the subepithelial space of the GBM in cases 1-4. In case 5, EDD were present in the mesangium and the subendothelial space of the GBM, as well as in the subepithelial space. After treatment with immunosuppressants (prednisolone and/or cyclosporin) or angiotensin-converting enzyme inhibitors, complete remission with disappearance of proteinuria was achieved 12.2 months in all 5 patients, but nephrotic range proteinuria relapsed in two patients during follow up. Serum anti-PLA2R autoantibody was negative in three patients. HSCT-related MGN only occurred after umbilical cord blood transplantation (UCBT). We believe that there were two morphologic patterns; early MGN and membranoproliferative pattern glomerulonephritis.
Background Hepatic transcatheter arterial embolization (TAE) has become an accepted treatment option for patients with symptomatic autosomal dominant polycystic kidney disease (ADPKD) who also have ...polycystic liver disease and who are not good candidates for surgery. However, indications for TAE and long-term outcome with it are still unclear. Study Design Retrospective cohort study. Setting & Participants Symptomatic patients with ADPKD with polycystic liver disease who underwent hepatic TAE, June 2001 to December 2012, at Toranomon Hospital and whose liver volume data were available were studied (N = 244; 56% on dialysis therapy, none with kidney transplants). Mean age was 55 ± 9 (SD) years, and mean liver volumes were 8,353 ± 2,807 and 6,626 ± 2,485 cm3 in men and women, respectively. Target arteries were embolized from the periphery using platinum microcoils. Predictors Sex-specific quartiles (6,433, 8,142, and 9,574 cm3 in men and 4,638, 6,078, and 8,181 cm3 in women) of total liver volume pretreatment. Outcomes All causes of mortality were obtained from medical records, followed up until July 31, 2013. Measurements Laboratory values were measured before TAE and 1, 3, 6, and 12 months after. Organ volumes were measured pretreatment, then 6 and 12 months after, by summing the products of the organ areas traced in each computed tomographic image. Results Liver/cyst volume decreased to 94.7% (95% CI, 93.5%-95.8%) at 6 months and 90.8% (95% CI, 88.7%-92.9%) at 12 months of pretreatment volumes. Serum protein and hematocrit values improved significantly without liver damage. Survival was significantly better for patients with liver volume ≤ 9,574 cm3 (men) and ≤8,181 cm3 (women) than for those with larger livers (5-year survival, 69% and 48%; P = 0.02). Infection and liver failure caused most deaths, especially in patients with larger livers. Limitations Referral bias and lack of control group. Conclusions Hepatic TAE appears to be a safe and less invasive option for patients with symptomatic polycystic liver, especially those contraindicated for surgical treatment (eg, with malnutrition or on dialysis therapy), improving both hepatic volume and nutrition.
Summary A 35-year-old woman was admitted to our hospital for evaluation of end-stage renal failure. Diagnostic imaging, including ultrasonography and magnetic resonance imaging, showed polycystic ...kidneys and peribiliary hepatic cysts, but the renal cysts were isointense and her kidneys were smaller than the end-stage kidneys of patients with autosomal dominant polycystic kidney disease. Glomerulocystic kidney disease was diagnosed by renal biopsy. Clinical examination revealed findings such as a missing maxillary canine, lingual anomalies, and brachydactyly. Genetic testing gave a diagnosis of orofaciodigital syndrome type 1 with a 5 nucleotide deletion indicating a frameshift mutation in exon 9. The patient's mother had the same mutation and similar clinical findings. This case is useful for understanding kidney and liver involvement in orofaciodigital syndrome type 1.
Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a recently described disease entity. In the kidney transplantation literature, only 6 recurrent and 2 de ...novo PGNMID cases, including 7 of the IgG3 subclass (6 with κ light chain and 1 with λ light chain) and 1 of the IgG1 subclass (λ light chain), have been described to date. We describe a 52-year-old man with end-stage renal disease whose primary glomerular disease had been suggested to be membranoproliferative glomerulonephritis. The patient underwent living related donor kidney transplantation and presented with proteinuria, hematuria, and decreased kidney function at 4 months posttransplantation. Biopsy of the transplanted kidney showed diffuse endocapillary proliferative glomerulonephritis. Immunofluorescence microscopy showed prominent granular glomerular staining for IgG, C3, and λ light chain, with IgM, IgA, and κ light chain undetectable. Immunofluorescence staining for IgG subclass showed signal for IgG2 only. Retrospective analysis of the native kidney biopsy specimen also showed the same monoclonal glomerular staining for the IgG2λ subtype. These findings led us to the diagnosis of PGNMID of the IgG2λ subtype as both the primary glomerular disease and recurrent disease in the transplanted kidney. Recurrence was treated with high-dose prednisolone, which decreased proteinuria, hematuria, and serum creatinine level. The case demonstrates that PGNMID of the IgG2λ subtype also can recur in the transplanted kidney.
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