Bajema, I.M.

The clinical relevance of a repeat biopsy in lupus nephritis flares (Article)

2009-12-01T00:00:00Z

Background. The clinical utility of performing repeat biopsies during lupus nephritis flares is questionable and data pointing towards frequent class switches are based on the old WHO classification. This retrospective study investigates the hypothesis that clinically relevant switches from proliferative to non-proliferative lesions and vice versa as determined by the new ISNRPS classification are a rare event and that repeat biopsies are unnecessary in many cases.Methods. Thirty-five patients with lupus nephritis and one or more repeat renal biopsies were included. Eighty-four biopsies were blindly reassessed according to the ISNRPS classification.Results. Twenty-five patients had one repeat biopsy, 6 patients had two and 4 patients had three repeat biopsies. Forty-nine comparisons between reference and repeat biopsies could be made. In 25 cases (54.3), there was no shift in ISNRPS class on repeat biopsies. In 41 instances, paired biopsies showed proliferative lesions both on reference and repeat biopsies, whereas five of six cases with non-proliferative lesions on a reference biopsy switched to proliferative lesions on a repeat biopsy. Clinically significant class switches during lupus nephritis flares were more frequent in patients with non-proliferative lesions in their reference biopsy (P < 0.001).Conclusion. The results show that patients with proliferative lesions in the original biopsy rarely switch to a pure non-proliferative nephritis during a flare. Therefore, a repeat biopsy during a lupus nephritis flare is frequently not necessary if proliferative lesions were found in the reference biopsy. However, in the case of a non-proliferative lesion in the reference biopsy, class switches are frequently found and repeat biopsies are advisable.

Congenital DNA repair deficiency results in protection against renal ischemia reperfusion injury in mice (Article)

2009-04-07T00:00:00Z

Cockayne syndrome and other segmental progerias with inborn defects in DNA repair mechanisms are thought to be due in part to hypersensitivity to endogenous oxidative DNA damage. The accelerated aging-like symptoms of this disorder include dysmyelination within the central nervous system, progressive sensineuronal hearing loss and retinal degeneration. We tested the effects of congenital nucleotide excision DNA repair deficiency on acute oxidative stress sensitivity in vivo. Surprisingly, we found mouse models of Cockayne syndrome less susceptible than wild type animals to surgically induced renal ischemia reperfusion injury, a multifactorial injury mediated in part by oxidative damage. Renal failure-related mortality was significantly reduced in Csb-/-mice, kidney function was improved and proliferation was significantly higher in the regenerative phase following ischemic injury. Protection from ischemic damage correlated with improved baseline glucose tolerance and insulin sensitivity and a reduced inflammatory response following injury. Protection was further associated with genetic ablation of a different Cockayne syndrome-associated gene, Csa. Our data provide the first functional in vivo evidence that congenital DNA repair deficiency can induce protection from acute stress in at least one organ. This suggests that while specific types of unrepaired endogenous DNA damage may lead to detrimental effects in certain tissues, they may at the same time elicit beneficial adaptive changes in others and thus contribute to the tissue specificity of disease symptoms. © 2009 The Authors Journal compilation

Fidelity and evolution of recurrent FSGS in renal allografts (Article)

2008-11-01T00:00:00Z

Five pathologic variants of FSGS were recently defined ("Columbia classification"), but the stability of these phenotypes in renal allografts remains unknown. We hypothesized that if the variants represent distinct diseases, then the pattern of recurrent FSGS in renal allografts will mimic the original disease in the native kidney. This multicenter study included 21 cases of recurrent FSGS from 19 patients who had both native and transplant biopsy samples available for analysis. These results support the Columbia classification, because 81% recurred in the same pattern as the original disease, but three variants manifested plasticity from native to allograft kidneys or in the pattern of recurrence (four FSGS, not otherwise specified [NOS] to collapsing variant, two collapsing variant to FSGS NOS, and one cellular variant to FSGS NOS). No transitions between the cellular and the collapsing variants were observed, supporting the view that these are separate entities. Three categories of recurrence were observed: Type I, recurrence of the same variant of FSGS; type II, recurrence of the same FSGS variant, preceded by a minimal change-like lesion; and type III, recurrence of a different FSGS variant in the allograft. Thus, potential evolution of the pathologic phenotype should be considered in pathologic interpretation and clinical trials. Copyright

Quantification of dendritic cell subsets in human renal tissue under normal and pathological conditions (Article)

2007-05-14T00:00:00Z

Dendritic cells (DCs) play critical roles in immune responses and can be distinguished in two major subsets, myeloid and plasmacytoid DCs. Although the presence of DC in all peripheral organs, including the kidney, has been well documented, no accurate estimates of DC subsets in human kidneys have been reported. This study shows a detailed analysis of DC subsets in cryosections of human renal tissue. The cortex of normal kidneys contains at least two different HLA-DR+myeloid DC subtypes characterized by BDCA-1+DC-SIGN+and BDCA-1+DC-SIGN-. The staining for DC-SIGN completely overlapped with CD68 in the renal interstitium. Unexpectedly, BDCA-2+DC-SIGN-plasmacytoid DCs are also abundantly present. Both subsets are located in the tubulo-interstitium often with a high frequency around, but rarely observed within glomeruli. Quantification of BDCA-1+, DC-SIGN+, and BDCA-2+cells in normal human renal tissue (pretransplant biopsy living donors; n=21) revealed that BDCA-1 is about four times as frequently present as BDCA-2. A preliminary cross-sectional analysis of DC in diseased kidneys, including rejection and immunoglobulin A nephropathy, revealed that the number of DC as well as their anatomical distribution might change under pathophysiological conditions. In conclusion, we show that human kidneys contain a dense network of myeloid and plasmacytoid DCs and provide the tools for phenotyping and enumeration of these cells to better understand interindividual differences in immune responses.

Long-term impact of pneumoperitoneum used for laparoscopic donor nephrectomy on renal function and histomorphology in donor and recipient rats. (Article)

2003-01-01T00:00:00Z

OBJECTIVE: To investigate the long-term impact of pneumoperitoneum used for laparoscopic donor nephrectomy on renal function and histomorphology in donor and recipient. SUMMARY BACKGROUND DATA: Laparoscopic donor nephrectomy has the potential to increase the number of living kidney donations by reducing donor morbidity. However, function of laparoscopically procured kidneys might be at risk due to ischemia as a consequence of elevated intra-abdominal pressure during laparoscopy. METHODS: In experiment 1, 30 Brown Norway rats were randomized to three procedures: 2 hours of CO2 insufflation, 2 hours of helium insufflation, and 2 hours of gasless laparoscopy. After this, a unilateral nephrectomy was performed in all animals. Another six rats were used as controls. In experiment 2, 36 donor Brown Norway rats were subjected to a similar insufflation protocol, but after nephrectomy a syngeneic renal transplantation was performed. All rats had a follow-up period of 12 months. Urine and blood samples were collected each month for determination of renal function. After 1 year, donor and recipient kidneys were removed for histomorphologic and immunohistochemical analysis. RESULTS: In donors as well as in recipients, no significant changes in serum creatinine, proteinuria, or glomerular filtration rate were detected between the CO2, the helium, and the gasless control group after 1 year. No histologic abnormalities due to abdominal gas insufflation were found. Immunohistochemical analysis did not show significant differences in the number of infiltrating cells (CD4, CD8, ED1, OX62, and OX6) and adhesion molecule expression (ICAM-1) between the three groups. CONCLUSIONS: Abdominal gas insufflation does not impair renal function in the donor 1 year after LDN. One year after transplantation, no differences in renal function or histomorphology were detected between kidney grafts exposed to either pneumoperitoneum or a gasless procedure.