Elizabeth C. Lorenz

Recurrent membranoproliferative glomerulonephritis after kidney transplantation

On examination of the records of 1321 patients following kidney transplant over an 11-year period, we found that 29 patients had recurrent membranoproliferative glomerulonephritis (MPGN). We excluded from this analysis patients who had MPGN type II, those with clear evidence of secondary MPGN, and those lacking post-transplant biopsies. During an average of 53 months of follow-up, we found using protocol biopsies that 12 of these patients had recurrent MPGN diagnosed 1 week to 14 months post-transplant. In 4 of the 12 patients this presented clinically, whereas the remaining had subclinical disease. The risk of recurrence was significantly increased in patients with low complement levels. Serum monoclonal proteins were found in a total of six patients; appeared to be associated with earlier, more aggressive disease; and were more common in recurrent than non-recurrent disease. The recurrence of MPGN was marginally higher in recipients of living-donor kidneys. Some patients developed characteristic lesions within 2 months post-transplant, whereas others presented with minimal, atypical histological changes that progressed to MPGN. Of 29 patients, 5 lost their allograft and 2 patients remain on chronic plasmapheresis. Our study shows the risk of MPGN recurrence and progression depends on identifiable pretransplant characteristics, has variable clinical impact, and can result in graft failure.

Long-term outcome of autologous stem cell transplantation in light chain deposition disease

BACKGROUND Light chain deposition disease (LCDD) is a systemic disorder characterized by deposition of non-amyloid monoclonal light chains. Renal dysfunction is a ubiquitous manifestation of the LCDD disease. Reports suggest that high-dose chemotherapy and autologous stem cell transplantation (ASCT) may be beneficial in the treatment of LCDD. However, the impact of ASCT on renal function is unclear. This study retrospectively reviewed the effect of ASCT on renal function in patients with LCDD. METHODS Six patients with LCDD have been transplanted at our institution since 2001. Patients received dexamethasone alone, dexamethasone plus thalidomide or no chemotherapy prior to conditioning. All the patients underwent high-dose melphalan conditioning after stem cell mobilization. RESULTS Three of the six patients had concurrent multiple myeloma (MM), and one patient was on haemodialysis prior to transplantation. Four patients were male and two were female. The median age was 43.5 years with a median serum creatinine of 2.4 mg/dl and a median estimated glomerular filtration rate (eGFR) of 26.5 ml/min/1.73 m(2). Five patients survived ASCT and one died on Day 26 of transplantation. Median follow-up was 31.7 months (range 31.3-60.7 months) after ASCT. Of the surviving patients, all the five achieved a haematological response post-transplantation although two ultimately relapsed and required further chemotherapy. The eGFR of one patient declined with relapse and improved with treatment, while the eGFR of the second patient remained stable throughout relapse and treatment. The patient on haemodialysis prior to transplantation continued to require it afterward, but ultimately received a renal transplant. Median reduction in proteinuria was 92% and median improvement in eGFR was 95%. Of the four evaluable patients all achieved criteria for a renal response after ASCT. CONCLUSIONS ASCT may be an effective therapy for renal dysfunction associated with LCDD. In cases where kidney dysfunction persists after ASCT, a haematological response may permit successful kidney transplantation with improved graft viability and decreased risk of recurrence.

Prevalence of Renal Artery and Kidney Abnormalities by Computed Tomography among Healthy Adults

BACKGROUND AND OBJECTIVES Management of incidental renal artery and kidney abnormalities in patients undergoing computed tomography scans is a clinical challenge because their frequency in healthy subjects has not been precisely estimated. Therefore, the prevalence and management of these abnormalities were determined among a large cohort of potential kidney donors undergoing protocol evaluations. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS All patients at the Mayo Clinic who underwent computed tomographic angiography and urography as part of their kidney donor evaluation between 2000 and 2008 were identified. Radiographic reports were abstracted for abnormalities of the renal arteries and kidneys. The prevalence of radiographic abnormalities was stratified by age and gender, and the effect on approval for kidney donation was determined. RESULTS Among 1957 potential kidney donors, the mean +/- SD age was 43 +/- 12 years, and 58% were women. The most common abnormalities were kidney stones (11%), focal scarring (3.6%), fibromuscular dysplasia (2.8%), and other renal artery narrowing or atherosclerosis (5.3%). Fibromuscular dysplasia, focal scarring, parenchymal atrophy, and upper tract dilation were more common in women. Renal artery narrowing, focal scarring, and indeterminate masses increased with age. Overall, 25% of potential donors had at least one abnormality. However, these incidental radiographic abnormalities contributed to exclusion from donation in only 6.7% of potential donors. CONCLUSIONS Incidental radiographic abnormalities of the renal arteries and kidneys are common. The majority of imaging findings are not perceived to be harmful enough to prevent kidney donation, but future studies are needed to determine their clinical relevance.

Clinical Findings, Pathology, and Outcomes of C3GN after Kidney Transplantation

C3 glomerulonephritis (C3GN) results from abnormalities in the alternative pathway of complement, and it is characterized by deposition of C3 with absent or scant Ig deposition. In many patients, C3GN progresses to ESRD. The clinical features, pathology, and outcomes of patients with C3GN receiving kidney transplantation are unknown. Between 1996 and 2010, we identified 21 patients at our institution who received a kidney transplant because of ESRD from C3GN. The median age at the time of initial diagnosis of C3GN at kidney biopsy was 20.8 years. The median time from native kidney biopsy to dialysis or transplantation was 42.3 months. Of 21 patients, 14 (66.7%) patients developed recurrent C3GN in the allograft. The median time to recurrence of disease was 28 months. Graft failure occurred in 50% of patients with recurrent C3GN, with a median time of 77 months to graft failure post-transplantation. The remaining 50% of patients had functioning grafts, with a median follow-up of 73.9 months. The majority of patients had hematuria and proteinuria at time of recurrence. Three (21%) patients were positive for monoclonal gammopathy and had a faster rate of recurrence and graft loss. Kidney biopsy at the time of recurrence showed mesangial proliferative GN in eight patients and membranoproliferative GN in six patients. All allograft kidney biopsies showed bright C3 staining (2-3+), with six biopsies also showing trace/1+ staining for IgM and/or IgG. To summarize, C3GN recurs in 66.7% of patients, and one half of the patients experience graft failure caused by recurrence.

Significance and implications of capillaritis during acute rejection of kidney allografts.

Background. Anti-human leukocyte antigen antibodies (a-HLA) cause graft injury identified by C4d in peritubular capillaries. We investigated whether a-HLA relate to episodes of C4d negative acute rejection (AR). Methods. We analyzed 878 kidney recipients transplanted from January 2000 to December 2006. Pretransplant, 36% of these crossmatch negative recipients had a-HLA measured by solid phase assays. Results. AR occurred in 154 patients (18%) and 11 of them (9.4%) were C4d+. Forty-six percent of ARs were diagnosed by protocol biopsy. The risk of C4d-AR was increased in patients with a-HLA class I with donor specificity (DSA-I) (hazard ratio=1.519; confidence interval, 1.02-2.26; P=0.039). DSA-II were not associated with an increased risk of C4d-AR. The relationship between DSA-I and C4d-AR was independent of recipient age, BK nephropathy, and HLA mismatches. Compared with DSA−, in DSA+ recipients C4d-AR were most often histologically “borderline.” DSA+ was associated with capillaritis in the biopsy (glomerulitis, 6.1% vs. 32%, P=0.003; peritubular capillaritis: 13% vs. 40%, P=0.0009). Compared with no AR, C4d-AR with capillaritis was associated with reduced graft survival (hazard ratio=4.164; confidence interval, 1.763-9.832; P=0.001), independent of other variables. This association was observed even in the cases of borderline AR. Conclusions. DSA-I increases the risk of C4d-AR. The presence of DSA-I or II is associated with capillaritis during AR. Capillaritis is associated with reduced graft survival.

Clinical characteristics of potential kidney donors with asymptomatic kidney stones

BACKGROUND Patients with symptomatic kidney stones are characterized by older age, male gender, white race, hypertension, obesity, metabolic syndrome and chronic kidney disease. Whether these characteristics differ in patients with asymptomatic kidney stones is unknown. METHODS All potential kidney donors who underwent protocol computed tomography angiograms/urograms (2000-08) at the Mayo Clinic were identified. Renal abnormalities, including kidney stones, were assessed radiographically. Comorbidities, including past symptomatic kidney stones, were abstracted from the medical record. Characteristics of persons with and without radiographic stones were compared. Stone burden among persons with and without past symptomatic stones was compared. RESULTS Among 1957 potential kidney donors, 3% had past symptomatic stones and 11% had radiographic stones (10% had only asymptomatic radiographic stones). Asymptomatic stone formers were more likely to be of white race, have low urine volumes and have radiographic findings of renal parenchymal thinning, focal renal scarring, medullary sponge kidney and polycystic kidney disease. Asymptomatic stone formers were not characterized by older age, male gender, hypertension, obesity, metabolic syndrome, abnormal kidney function, hyperuricemia, hypercalcemia or hypophosphatemia. Among persons with radiographic stones, those with past symptomatic stones had a slightly higher number of stones (mean 2.7 versus 2.4; P = 0.04), but a much greater diameter for the largest stone (mean 4.8 versus 1.6 mm; P < 0.001). CONCLUSIONS Asymptomatic kidney stone formers have different demographic characteristics and many lack the comorbidities that have been described in persons with symptomatic kidney stones. These findings suggest that different pathophysiologic mechanisms could be involved in asymptomatic stone formation versus symptomatic stone passage.

Patient Survival After Kidney Transplantation: Relationship to Pretransplant Cardiac Troponin T Levels

Assessing cardiovascular (CV) risk pretransplant is imprecise. We sought to determine whether cardiac troponin T (cTnT) relates to patient survival posttransplant. The study includes 603 adults, recipients of kidney transplants. In addition to cTnT dobutamine stress echography and coronary angiography were done in 45% and 19% of the candidates respectively. During 28.4 ± 12.9 months 5.6% of patients died or had a major cardiac event. cTnT levels were elevated (>0.01 ng/ml) in 56.2% of patients. Elevated cTnT related to reduced event‐free survival (hazard ratio (HR) = 1.81, CI 1.33–2.45, p < 0.0001) whether those events occurred during the first year or beyond. This relationship was statistically independent of all other variables tested, including older age, reduced left ventricular ejection fraction (EF) and delayed graft function. cTnT levels allowed better definition of risk in patients with other CV risk factors. Thus, event‐free survival was excellent in older individuals, patients with diabetes, low EF and those with preexisting heart disease if their cTnT levels were normal. However, elevated cTnT together with another CV risk factor(s) identified patient with very poor survival posttransplant. Pretransplant cTnT levels are strong and independent predictors of posttransplant survival. These results suggest that cTnT is quite helpful in CV risk stratification of kidney transplant recipients.

Update on Oxalate Crystal Disease

Oxalate arthropathy is a rare cause of arthritis characterized by deposition of calcium oxalate crystals within synovial fluid. This condition typically occurs in patients with underlying primary or secondary hyperoxaluria. Primary hyperoxaluria constitutes a group of genetic disorders resulting in endogenous overproduction of oxalate, whereas secondary hyperoxaluria results from gastrointestinal disorders associated with fat malabsorption and increased absorption of dietary oxalate. In both conditions, oxalate crystals can deposit in the kidney leading to renal failure. Since oxalate is primarily renally eliminated, it accumulates throughout the body in renal failure, a state termed oxalosis. Affected organs can include bones, joints, heart, eyes, and skin. Since patients can present with renal failure and oxalosis before the underlying diagnosis of hyperoxaluria has been made, it is important to consider hyperoxaluria in patients who present with unexplained soft tissue crystal deposition. The best treatment of oxalosis is prevention. If patients present with advanced disease, treatment of oxalate arthritis consists of symptom management and control of the underlying disease process.

Renal failure due to combined cast nephropathy, amyloidosis and light-chain deposition disease.

Renal dysfunction commonly occurs in multiple myeloma (MM) and is caused by deposition of abnormal light chain within various compartments of the kidney. Renal pathologic findings are diverse and include cast nephropathy (CN), amyloidosis and light-chain deposition disease (LCDD). We report a case of renal failure in a patient with MM caused by concurrent CN, amyloidosis and LCDD which has not been previously described.

The impact of urinary tract infections in renal transplant recipients

Urinary tract infections (UTIs), including cystitis and pyelonephritis, are the most common infections after kidney transplantation. On examining the role of surveillance and treatment of asymptomatic bacteriuria posttransplant, Fiorante and colleagues found that up to 50% of recipients had bacteriuria. Despite routine treatment, recurrent UTIs remained common. Many risk factors contribute to the high incidence of UTIs, which can undermine graft function and survival. Given that many UTIs are asymptomatic, screening protocols may be beneficial.