Primary cilia metaplasia in renal transplant biopsies with acute tubular injury.

Primary cilia are hair-like organelles singly distributed along the apical surface of proximal and distal nephron tubules as mechanosensors. The goal of this study was to use electron microscopy to systemically evaluate cilia changes in acute tubular injury (ATI) from both transplant and native renal biopsies. Three groups of cases were included: control group 1-native biopsies without major changes in renal tubules; study group 2-native biopsies with prominent ATI; and study group 3-renal transplant biopsies with prominent ATI (delayed renal function group). Extensive search for ciliary structures along renal tubules was conducted in each case, focused on proximal tubular areas with injured (diminished) apical microvilli. Singly located cilia were found in 3/19 specimens in control group 1, 4/18 in group 2 (native ATI), and 6/24 in group 3 (transplant ATI). Importantly, there were clusters of cilia in proximal tubules with markedly diminished apical microvilli in 3/24 biopsies from 2 patients in group 3, but none from groups 1 and 2. The clusters of cilia ranged from 6 to 15 individual cilia along the apical surface with diminished apical microvilli. Under high magnifications, the cilia demonstrated 9 pairs of peripheral microtubules without a central pair of microtubules, consistent with primary cilia (9 + 0) rather than motile cilia (9 + 2). In summary, the authors found clusters of cilia in proximal tubules with remarkable apical microvillar injury in 3 renal transplant biopsies with ATI, implying a reactive, or repairing, process following tubular injury, thus they name this finding "cilia metaplasia".

Adjuvant role of p53 immunostaining in detecting BK viral infection in renal allograft biopsies.

BK virus infection is a significant threat to renal transplant outcome. Detecting viral infection in renal transplant biopsies using SV40 staining is less than ideal. SV40 antibody reacts with the large T-antigen of BK virus only at the early phases of infection and can miss cells in later stages of infection. As p53 is upregulated during both early and late phases of infection, this study set out to determine whether p53 staining could improve detection of BK virus infection in renal transplant patients. The control group consisted of 16 renal allograft biopsies without histologic evidence of BK virus infection, while the BK group consisted of 15 renal allograft biopsies with histologic evidence of BK virus infection. The biopsies from both groups were immunohistochemically stained with both SV40 and p53 antibodies. Dual staining with both markers was also performed to identify their nuclear co-localization. In the BK group, the percent of p53 staining (16.6 ± 4.8 %) was significantly higher than the percent of SV40 staining (5.4 ± 2.7%). BK virus infected cells revealed a unique p53 immunostaining pattern (strong nuclear staining with a central halo). Co-localization of SV40 and p53 was identified in cells that had characteristic nuclear features of BK virus infection by histology. The sensitivity and specificity for using p53 staining to identify BK infected cells was 92% and 86 %, respectively. In conclusion, p53 staining detects a higher percentage of BK virus infected cells than SV40 staining alone. Thus, for diagnosis of BK virus infection in renal allograft biopsies, p53 staining is a sensitive and specific method when used along with SV40 staining.

Relation between degree of weight loss after bariatric surgery and reduction in albuminuria and C-reactive protein.

BACKGROUND: Bariatric surgery achieves long-term weight loss in obese adults with amelioration of diabetes and hypertension. Improvement in albuminuria and high-sensitivity C-reactive protein (hs-CRP) has also been reported. We investigated, at a weight control center in a community hospital setting, the relation between degree of surgical weight loss and reduction in the cardiovascular risk markers, albuminuria and hs-CRP. METHODS: We performed a retrospective study of 62 obese adults who had undergone Roux-en-Y gastric bypass surgery and had a median follow-up of 15 months. RESULTS: The baseline (preoperative) mean age was 46 years, 82% were women, 26 had a blood pressure of > or =140/90 mm Hg, and 25 had type 2 diabetes. During follow-up (postoperative), a decrease occurred in the body mass index (mean +/- standard deviation 49.2 +/- 8.7 kg/m(2) to 34.1 +/- 8.1 kg/m(2); P <.0001), excess body weight (mean +/- SD 76.1 +/- 23.6 kg to 34.9 +/- 21.7 kg; P <.0001), hemoglobin A1c (mean +/- SD 6.5% +/- 1.3% to 5.6% +/- 0.8%; P <.0001), systolic blood pressure (mean +/- SD 133.7 +/- 14.3 mm Hg to 112.9 +/- 14.6 mm Hg; P < .0001), urine albumin creatinine ratio (from a median of 8.0 mg/g [interquartile range 5.0-29.3] to a median of 6.0 mg/g [interquartile range 3.3-11.5]; P <.0001), and hs-CRP (mean +/- SD 11.2 +/- 9.8 mg/L to 4.7 +/- 5.9 mg/L; P <.0001). The study sample was divided into tertiles of the percentage of excess body weight loss; the mean percentage of excess body weight loss was -37.1% +/- 5.5% in the first tertile, -54.3% +/- 6.8% in the second tertile, and -75.8% +/- 10.9% in the third tertile. The median percentage of change in albuminuria was greatest (median -52.8%, interquartile range -79.1% to -17.5%) in the third tertile, intermediate (median -45.5%, interquartile range -72.4% to 0%) in the second tertile, and lowest (-42.6%, interquartile range -80.5% to 16.7%) in the first tertile (P = .953). The mean percentage of change in hs-CRP was greatest (-72.4% +/- 30.4%) in the third tertile, intermediate (-55.4% +/- 31.9%) in the second tertile, and lowest (-44.8% +/- 30.6%) in the first tertile (P = .037). CONCLUSION: The results of our study have shown that obese adults experience a reduction in albuminuria and hs-CRP after bariatric surgery, with a greater reduction in hs-CRP observed with more surgical weight loss.

Impact of kidney transplantation on the progression of cardiovascular disease.

Kidney transplantation, of all the treatment modalities for end-stage renal disease, affords the greatest potential for prolonged survival and improved quality of life. Great strides in immunosuppressant therapy have improved graft survival and forced clinicians to consider other health-care needs of kidney transplant recipients. Chief among these needs is the prevention and treatment of cardiovascular disease. Cardiovascular disease is the most common cause of death among patients with a working renal allograft. Because therapies for primary and secondary prevention are successful in the general population, transplant clinicians are increasingly focused on preventing or limiting the progression of cardiovascular disease. Initiation of aggressive management of conventional atherosclerotic risk factors and uremia-related risk factors, ideally during the early stages of chronic kidney disease (CKD) or after kidney transplantation, and efforts to delay the progression of kidney disease will hopefully reduce the cardiovascular burden in transplant recipients.