Renal Involvement in IgG4-Related Disease: From Sunlight to Twilight.

IgG4-Related Disease (IgG4-RD) is a fibroinflammatory condition characterized by a typical histopathological pattern (dense lymphoplasmacytic infiltrate with prevalent IgG4+ plasma cells and storiform fibrosis), which may involve the kidney both directly (IgG4-related kidney disease, IgG4-RKD) or indirectly, as a consequence of post-renal ureteral obstruction due to retroperitoneal fibrosis (IgG4-RD RF). The most frequent presentation of IgG4-RKD is IgG4-related tubulointerstitial nephritis (TIN), but a glomerular disease can be present, in most of the cases a membranous nephropathy. Albeit steroid-responsive, in some cases renal manifestations may lead to progressive and permanent organ damage. In this review we describe four clinical cases representative of typical and less typical renal manifestations of IgG4-RD, emphasizing a potential, subclinical, early involvement of the kidney in the disease.

Home blood pressure measurement as a systematic tool for clinical practice in CKD patients: a real-world picture.

BACKGROUND: Arterial hypertension is very common in chronic kidney disease (CKD) patients and its prevalence increases with lowering estimated glomerular filtration rate (eGFR). Blood pressure (BP) control is a cornerstone in the treatment of CKD patients but still most treatment decisions are based on office BP measurement (OBPM). The aim of this cross-sectional, retrospective study is to investigate the prevalence of hypertension phenotypes in CKD patients and whether different home (HBPM) or OBPM are associated with a different CKD stage and cardiovascular comorbidities. METHODS: We analyzed 560 consecutive patients (359 men, age 70±13 years), affected by stage 3-5 CKD, who performed HBPM recording; OBPM during a single visit was also assessed. Uncontrolled hypertension was defined as OBPM values ≥140/90 mmHg and HBPM values ≥135/85 mmHg, respectively. RESULTS: Systolic and diastolic HBPM values were lower than OBPM values. A white coat effect (systolic BP +18±12 mmHg) was detected in 62.5%, while a masked effect (systolic BP -14±10 mmHg) was detected in 22.7%. No relationship was found between BP differences and body weight, CKD stage, eGFR or presence of diabetes. Based on OBPM, 18.6% of patients showed controlled systolic and diastolic BP, whereas 37.8% had sustained hypertension. White-coat hypertension was detected in 23.4% and Masked hypertension in 12.1%. The multiple logistic regression model showed that masked uncontrolled hypertensive patients showed a higher probability of having ischemic heart disease (OR=2.54 [1.02-6.36]), while sustained hypertension was associated with an increased prevalence of stroke in comparison to normotensive or true control BP group (OR=4.72 [1.30-17.07]). Age, gender, diabetes or CKD stage, were not different among the four hypertension phenotypes. CONCLUSIONS: We observed a quite high rate of masked uncontrolled hypertension and of white coat hypertension in stage 3-5ND CKD patients. Office BP measurement, as a single tool, is an inadequate diagnostic procedure in the clinical management of CKD patients. HBPM should be routinely implemented for identifying hypertensive phenotypes and then for avoiding misdiagnosis and mistreatment of pre-dialysis CKD patients in a tertiary care setting.

Nutrition and physical activity in CKD patients.

Chronic kidney disease (CKD) patients are at risk for protein-energy wasting, abnormal body composition and impaired physical capacity. These complications lead to increased risk of hospitalization, morbidity and mortality.In CKD patient as well as in healthy people, there is a close association between nutrition and physical activity. Namely, inadequate nutrient (energy) intake impairs physical performance thus favoring a sedentary lifestyle: this further contributes to loss of muscle strength and mass, which limit the quality of life and rehabilitation of CKD patients. In CKD as well as in end-stage-renal-disease patients, regular physical activity coupled with adequate energy and protein intake counteracts protein-energy wasting and related comorbidity and mortality. In summary, exercise training can positively influence nutritional status and the perception of well-being of CKD patients and may facilitate the anabolic effects of nutritional interventions.

Inflammatory biomarkers, glycemic variability, hypoglycemia, and renal transplant outcomes: results of a randomized controlled trial.

BACKGROUND: We previously reported that compared to standard glycemic control [blood glucose (BG): 70-180 mg/dL], patients randomized to intensive glycemic control (BG: 70-110 mg/dL) were at increased risk of graft rejection in renal transplantation. However, the underlying mechanisms that associate the effect of intensive glycemic control with renal transplant outcomes have not been identified. METHODS: A secondary data analysis of 93 participants (n=44 intensive, n=49 control) was conducted using data from a previous randomized controlled clinical trial. We examined inflammatory biomarkers, glycemic variability, hypoglycemia, and hyperglycemia as potential contributing etiologies by assessing the effect of intensive glycemic control on these characteristics, and evaluate the association of these variables with graft rejection. RESULTS: Intensive glycemic control had no appreciable effect on highly sensitive C-reactive protein, interleukin (IL)-6, tumor necrosis factor alpha, IL-1ß, or IL-10 levels at all time points after transplantation. Moreover, neither inflammatory biomarkers nor increased glycemic variability were associated with graft rejection. However, intensive treatment increased the risk of hypoglycemia (BG <70 mg/dL, 84% vs. 25%, P<0.001). In sub-analysis, compared to non-rejecters, rejecters demonstrated higher rates of blood glucose below 70 mg/dL (90% vs. 49%, P=0.02). CONCLUSION: Inflammatory biomarkers and increased glycemic variability lack correlation with clinical outcomes in renal transplant, but importantly, increased perioperative hypoglycemic episodes (BG <70mg/dL) may be a salient etiology that contributed to the increased risk for acute allograft rejection related to intensive glycemic control. Further research is needed to confirm a causal association.

A randomized controlled trial to evaluate the effect of glycemic control on renal transplantation outcomes.

CONTEXT: Outcomes from intensive glycemic control postrenal transplant have not been studied. OBJECTIVE: Our objective was to observe the optimal management of hyperglycemia in patients with diabetes or impaired glucose tolerance receiving renal transplantation. DESIGN, SETTING, AND PATIENTS: We conducted a randomized controlled trial with patients undergoing renal transplantation randomized to either i.v. insulin therapy (intensive) or standard s.c. insulin therapy while the patients were admitted to the hospital. INTERVENTIONS: The study consisted of a 3-day postrenal transplant group treated with intensive i.v. insulin [blood glucose (BG) = 70-110 mg/dl] or a control group treated with s.c. insulin (BG = 70-180 mg/dl). MAIN OUTCOME MEASURE: The primary endpoint was delayed graft function (DGF). Secondary endpoints were glycemic control, graft survival, and acute rejection episodes. RESULTS: A total of 104 patients were screened and randomized to either the intensive or control condition; however, the intention-to-treat analysis set consisted of only the 93 participants (n = 44 intensive, n = 49 control) that underwent a renal transplant. DGF was present in 18% (eight of 44) of the intensive group and 24% (12 of 49) of the control group (P = 0.46). The occurrence of severe hypoglycemia (BG < 40 mg/dl) and severe hyperglycemia (BG > 350 mg/dl) were the primary safety outcome measures. There were nine participants with hypoglycemia identified, seven of which (78%) were in the intensive treatment group (P = 0.08). There were 30 instances of hyperglycemia with five participants (11%) in the intensive group and 12 participants (24%) in the control group having at least one hyperglycemic event (P = 0.10). For the 11 rejection episodes, nine were in the intensive treatment group (P = 0.013). CONCLUSIONS: The primary outcome measure of DGF was not statistically different for the two treatment groups. Regarding longer-term rejection and graft survival, the intensively treated participants were at higher risk for a rejection episode.

Can preemptive cytomegalovirus monitoring be as effective as universal prophylaxis when implemented as the standard of care in patients at moderate risk?

BACKGROUND: Cytomegalovirus (CMV) is a significant cause of morbidity, mortality, and cost in solid organ transplant recipients. This study was conducted to measure both the clinical efficacy and the pharmacoeconomic impact of implementing, as standard of care, an abbreviated preemptive monitoring strategy compared with universal prophylaxis in a large teaching hospital. METHODS: This prospective observational study included only recipients at moderate risk for CMV infection, specifically recipients who were CMV seropositive before transplant. Recipients transplanted between February 2006 and December 2006 received prophylactic valganciclovir for 90 days after transplant, and those transplanted between January 2007 and December 2007 were enrolled in a preemptive monitoring strategy that included no anti-CMV prophylaxis but instead used serial CMV polymerase chain reactions in weeks 4, 6, 8, 10, 12, 16, 20, and 24 to monitor the development of CMV DNAemia. Costs were analyzed from a societal perspective. RESULTS: A total of 130 patients were included in this study. Baseline and transplant demographics are well matched between groups. CMV syndrome occurred in three patients in each group, and one patient in the preemptive group developed CMV disease. Thirty-seven percent of patients in the preemptive group developed CMV DNAemia, 68% of these patients received antiviral therapy. Personnel and laboratory monitoring costs were significantly higher in the preemptive group, whereas medication cost was significantly higher in the prophylaxis group. CONCLUSIONS: Although outcomes and the overall cost of (1) universal prophylaxis and (2) preemptive monitoring are similar, universal prophylaxis places the cost burden on the patient whereas preemptive monitoring shifts the cost burden to the healthcare system.

Efficacy of induction therapy on acute rejection and graft outcomes in African American kidney transplantation.

BACKGROUND: African Americans (AA) have higher rejection rates and poorer graft outcomes compared to non-AAs. Induction therapy is yet unproven in this high risk population. METHODS: This retrospective study compared the efficacy of induction therapy [IL-2 receptor antibodies (IL2RA) or thymoglobulin] vs. no induction. RESULTS: One hundred and seventy-five AA patients were included in this analysis. Patients were well matched for demographic and immunologic characteristics in the non-induction and IL2RA induction groups; the Thymoglobulin induction group had significantly higher risk patients. Significantly fewer episodes of acute rejection occurred at one yr in patients treated with thymoglobulin and IL2RA vs. no induction (18% vs. 47%, p = 0.003, 26% vs. 47%, p = 0.02). Three yr graft survival was significantly improved in the IL2RA group compared to the non-induction group (85% vs. 68%, p = 0.032). Despite the thymoglobulin group being at high risk, they had similar graft survival rates compared to both the IL2RA group (76% vs. 85%, p = 0.18) and the non-induction group (76% vs. 68%, p = 0.48). Multivariate analysis demonstrated that induction therapy (combining IL2RA and thymoglobulin) independently reduced the risk of both acute rejection and graft loss. CONCLUSION: The use and type of induction therapy in AA patients significantly reduces acute rejection rates and may improve long-term graft outcomes in AA patients.

Comparison of efficacy of induction therapy in low immunologic risk African-American kidney transplant recipients.

African-Americans (AA) have higher acute rejection rates and poorer long-term graft survival rates when compared with non-AA. It is yet to be demonstrated that the type of induction therapy modifies outcomes in this 'high-risk' population. This retrospective analysis compares the efficacy of induction therapy [antilymphocyte antibodies (ALA) versus interleukin-2 receptor antagonists (IL-2RA)] in the AA population. Some 189 AAs were included. There was no difference in acute rejection at one year between the groups (ALA (12%) or IL-2RA (12%), P = 0.89). Type of induction therapy had no significant effect on death-censored (P = 0.61) or uncensored graft survival (P = 0.32). There was no difference between CMV or BK virus infections between the groups (P = 0.14 and 0.94 respectively). Type of induction therapy does not appear to affect acute rejection rates or long-term graft survival in low-risk AA kidney transplant recipients.

Risk factors and consequences of delayed graft function in deceased donor renal transplant patients receiving antithymocyte globulin induction.

BACKGROUND: Induction rabbit antithymocyte globulin (rATG) is largely used in renal allograft recipients at risk for delayed graft function (DGF) and immunologic rejection. The purpose of our study was to characterize risk factors and outcomes associated with DGF when it occurs in recipients undergoing routine rATG induction. METHODS: We retrospectively reviewed our experience in a predominantly high-risk population receiving modern immunosuppressive regimens. RESULTS: Of 231 deceased-donor transplants, high-risk characteristics included African American race (68%), retransplants (12%), peak panel reactive antibody of atleast 20% (19%), expanded criteria donor kidney (15%), and cold ischemia time exceeding 24 hr (27%). DGF occurred in 29% of patients. rATG was continued to a dose of 7.3 mg/kg in DGF patients and 5 mg/kg in non-DGF patients (P<0.0001). Risk factors for DGF were recipient body mass index greater than 30 kg/m(2) (odds ratio [OR]=1.5, P=0.02), female donor/male recipient pairings (OR=1.5, P=0.033), sirolimus use (OR=1.7, P=0.003), and donor creatinine more than 1.5 mg/dL (OR=1.6, P=0.016). One-year patient survival (99% non-DGF, 91% DGF; P=0.001) and acute rejection incidence through 36 months (11% non-DGF, 22.4% DGF; P=0.025) differed between groups. DGF patients experienced a higher rejection rate during the second and third years posttransplant. Death-censored graft survival was similar throughout 36 months. CONCLUSION: In kidney transplantation with routine rATG induction, DGF was related to size and gender, donor creatinine, and immunosuppressive protocol. Despite low first-year rejection rates, DGF was associated with inferior patient survival. Importantly, patients with DGF continued to be at risk for rejection beyond the first year. Donor and recipient selection impacts short-term outcomes, and induction alone may not confer a long-term advantage without further modification of baseline therapy.