BACKGROUND: The growing problem of relentless deterioration of renal function in patients who undergo transplantation of nonrenal solid organs is bound to have an increasingly important impact as it may not only worsen patient morbidity and mortality but also increase transplantation costs. METHODS: We reviewed the literature in order to provide a sum of the most important data on the incidence, clinical picture, renal pathology pattern, damage mechanisms, and risk factors, along with strategies for prevention and treatment of chronic renal damage following nonrenal solid organ transplantation. RESULTS: Literature data report that 10% to 80% of transplanted patients have some degree of renal dysfunction and that they share a common clinical picture characterized by relentless asymptomatic progression, frequent hypertension, mild urinary abnormalities, and pathology features of vascular, glomerular, tubular, and interstitial involvement. These changes are very similar to those reported for chronic nephrotoxicity from calcineurin inhibitors. The occurrence of end-stage renal disease (ESRD) requiring chronic dialysis has been reported in up to 20% of nonrenal transplant recipients. Although there are some organ-specific differences, a group of common risk factors has been recognized, including the use of calcineurin inhibitors as immunosuppressive agents, age, pretransplantation renal function, intraoperative/perioperative factors, concomitant use of other nephrotoxic drugs, infections, and posttransplantation acute renal failure. CONCLUSION: Calcineurin inhibitor-induced nephrotoxicity is a growing problem and, as the age of recipients of nonrenal organs is increasing, this problem is destined to increase. It would therefore be advisable for nephrologists to share their experiences in immunomodulation with other specialties, so as to favor the cautious extension of calcineurin inhibitor-sparing protocols to the area of life-saving transplants.

Humans↗

PubMed2004

Interaction between gene polymorphisms of nitric oxide synthase and renin-angiotensin system in the progression of membranous glomerulonephritis.

BACKGROUND: The renin-angiotensin system (RAS) and nitric oxide synthase (NOS) play a key role in the progression of primary glomerulonephritis (GN). Although previous studies have examined genetic risk associated with single gene variations, experiments assessing risk conferred by multiple gene variations are still scanty. METHODS: The effect of combination of variant alleles of four genes encoding for three components of the RAS [angiotensin converting enzyme insertion/deletion (ACE I/D), angiotensin II receptor 1 (AT1R 1166A/C), angiotensinogen (AGT M235T)] and for NOS (ecNOS4b/a) on the development and progression of membranous GN (MGN) were evaluated in a longitudinal study comparing 117 patients with serum creatinine (s-Cr) <1.5 mg/dl at renal biopsy and follow-up > or = 5 years (Kaplan-Meier and Cox multivariate analysis). The control group consisted of DNA from 171 organ donors. RESULTS: We found no relationship between single or combined variations of the four gene polymorphisms and development of MGN. Among single gene variations, there were no independent genetic risk factors for the progression of renal disease, after adjustment for age, sex, hypertension, proteinuria, s-Cr, chronicity and activity index. However, double variation coincidences such as the combination of the allele a of ecNOS4b/a and both the allele D of ACE I/D (chi(2) =4.80, P = 0.028; HR = 1.97, 95% CI 0.98-3.96) and the allele T of AGT (M235T) (chi(2) = 5.09, P = 0.024; HR = 2.84, 95% CI 1.39-5.82) exerted an additional effect that was higher than that of the single gene variations. CONCLUSION: This study is the first to demonstrate a role for an interaction between simultaneous variations of genes encoding for NOS and components of RAS in the progression of MGN. Interactions between various polymorphisms may explain conflicting results obtained in previous studies that examined single gene variations, since the effect of a single locus variation may be influenced by the simultaneous presence of other variant alleles in polygenic diseases such as primary GN. However, the small sample sizes and possible multiple interactions limited the interpretation of the current findings, which may represent true biological interaction or simply statistical interactions or spurious results due to the small sample sizes.

Adult↗

PubMed2004

How can we be sure that renal dysfunction after coronary angiography is just explained by contrast nephropathy?

Explore the source record for details and available documents.

Contrast Media↗

PubMedDate not supplied

IgM antibodies against cytomegalovirus in SLE nephritis: viral infection or aspecific autoantibody?

Despite many studies on the subject, the causal relationships between viruses and presentation/exacerbation of autoimmune diseases are still elusive. The possibility of false positive IgM antibody tests for human cytomegalovirus (CMV) in patients with systemic lupus erythematosus (SLE) has been pointed out. Here we report a case of a patient who developed lupus nephritis, with biochemical and clinical markers of CMV infection with intestinal involvement. At first, the antibodies to CMV were regarded as spurious aspecific signs of autoimmune disease. The patient had had serious flare-ups of the disease, hemolytic-uremic syndrome with thrombotic microangiopathy superimposed on SLE nephritis, and life-threatening infections for three years until CMV infection was confirmed by the persistence of anti-CMV IgM-antibodies coupled with positive results of tests for viral replication. After therapy with ganciclovir, his clinical and biochemical condition improved and remained stable for three years, with only very low maintenance steroid coupled with hydroxychloroquine. IgM anti-CMV were no longer detectable in spite of the persistence of other autoantibodies such as anti-DNA and ANA. Keeping in mind that CMV-IgM has been reported in only 5% of patients with SLE nephritis, the history of our patient indicates that CMV infection must be carefully excluded before IgM antibodies against CMV can be simply classified as an aspecific sign of cross-reacting autoantibodies formed in SLE patients.

Adult↗

PubMedDate not supplied

Selective stenting and the course of atherosclerotic renovascular nephropathy.

BACKGROUND: The effectiveness of percutaneous revascularisation (PTRA) in the treatment of atherosclerothic renovascular nephropathy (ARN), a leading cause of progressive renal failure, is still a matter of debate. METHODS: we reviewed 52 patients submitted to selective stenting from 1991 to 2000 because of ARN, followed for a mean of 22.3 months before and 24.6 after the procedure, looking for complications, re-stenosis rates, blood pressure, renal function and survival. RESULTS: Arterial patency was achieved in 97.1% of procedures (71.6% by stent deployment); complications occurred in 42% of patients, and re-stenoses in 17.3% of vessels, most often in those without a stent (31.6% vs 8.3%). No effect was detectable on hypertension and renal failure in the whole group, but in the subgroup without technical failure or early dialysis start PTRA reduced the creatinine clearance (BCRC) decline from 0.9 to 0.19 mL/min/month. At univariate analysis, BCRC outcome was better in bilateral or single kidney stenoses, proteinuria < 1 g/day, serum creatinine < 4 mg/dL and resistance index < 0.8. Survival was 68.9% at five years, with a mortality rate of 4.5/100 person-years. CONCLUSIONS: Renal outcome of successful PTRA differs from case to case, but efficacy is substantial. Primary stenting in ostial stenosis and selection of patients based on prognostic factors seem likely to improve the effectiveness.

Aged↗

PubMedDate not supplied

Pregnancy in kidney transplantation: satisfactory outcomes and harsh realities.

Since the first successful case of a pregnancy reported 40 yrs ago in a woman receiving a kidney transplant from her identical twin sister who did not receive immunosuppressive medications, the dream of a pregnancy in a renal transplant recipient has become reality. In women of childbearing age with a functioning transplant, the pregnancy rate has improved from 2 to 5%. Approximately 35% of pregnancies do not progress beyond the 1st trimester; the success rate is > 90% after the 1st trimester. In this review, different aspects of this topic are discussed: the consequences of pregnancy on renal grafts and maternal morbidity (hemodynamic changes, immunological problems, hypertension/preeclampsia, urinary tract infections and renal damage progression), the influence of renal grafts on pregnancy (perinatal mortality, prematurity, intrauterine growth retardation, low birth weight, malformations, handicaps and immunological problems) and the role of drugs used for renal transplants. A pregnancy can have a successful outcome if pre-conceptional graft function is good, if hypertension is absent and if the interval from grafting is at least 2 yrs. However, the majority of live-born outcomes are premature and many are low birth weight. Recipients must be advised that their offspring can also suffer from immunological abnormalities, malformations, long-term handicaps, and that the deleterious effects of pregnancy on long-term graft function cannot be excluded. In conclusion, women of childbearing age who have had renal transplantation should be counselled before conception about possibility and risks of pregnancy.

Congenital Abnormalities↗

PubMedDate not supplied

Pregnancy in patients with kidney disease.

QUESTIONS: - To what extent can ailing kidneys adapt their functions to the demands of pregnancy? - What risks is the nephropathic patient prone to throughout pregnancy compared with those of the general population, and which specific risks does her kidney disease determine? - What risks is the baby of a nephropathic prone to throughout pregnancy compared with those of the general population? - What changes have occurred over recent years? CONCLUSIONS: Current knowledge allows to conclude that pregnancy in the nephropathic woman can be started, provided that: - best timing is considered; - women are informed about their risk factors: functional levels and presence of hypertension, regardless of type of nephropathy.

Female↗