Role of microRNAs in kidney homeostasis and disease

MicroRNAs (miRNAs) are endogenous short (20-22 nucleotides) non-coding RNA molecules that mediate gene expression. This is an important regulatory mechanism to modulate fundamental cellular processes such as differentiation, proliferation, death, metabolism, and pathophysiology of many diseases. The miRNA expression profile of the kidney differs greatly from that of other organs, as well as between the different regions in the kidney. In kidneys, miRNAs are indispensable for development and homeostasis. In this review, we explore the involvement of miRNAs in the regulation of blood pressure, hormone, water, and ion balance pertaining to kidney homeostasis. We also highlight their importance in renal pathophysiology, such as in polycystic disease, diabetic nephropathy, nephrogenic diabetes insipidus, hypertension, renal cancer, and kidney fibrosis (epithelial-mesenchymal transition). In addition, we highlight the need for further investigations on miRNA-based studies in the development of diagnostic, prognostic, and therapeutic tools for renal diseases.     

Combined robotic lobectomy and adrenalectomy for lung cancer and solitary adrenal metastasis

Background and Objectives:

Surgical resection of isolated adrenal metastasis in primary lung cancer is associated with improved survival. We report a combined robotic lobectomy and adrenalectomy for resection of a primary lung cancer and metastasis to the adrenal gland.

Methods:

A 69-year-old male with a significant smoking history and shortness of breath was found to have a 3-cm left upper lobe mass with an enlarged left adrenal gland measuring 1.5cm. The adrenal gland was biopsied confirming metastatic poorly differentiated carcinoma, likely lung cancer. Computed tomography, positron emission tomography, and mediastinoscopy revealed no evidence of disease outside the adrenal gland.

Results:

Following induction chemotherapy, the patient underwent combination robotic lobectomy, lymphadenectomy, and adrenalectomy while in the same lateral decubitus position. Thoracic and urologic oncology teams performed their respective portions of the operation. Overall operative time was 4 hours, and length of hospital stay was 3 days. Estimated blood loss was 150mL with no narcotic requirements beyond the first postoperative day. Final pathology revealed large cell carcinoma of the lung with metastasis to the adrenal. All surgical margins were negative.

Conclusions:

Combination robotic lobectomy and adrenalectomy is feasible and can be associated with a short convalescence, minimal pain, and an oncologically sound approach.     

Strut allografts for failed treatment of periprosthetic femoral fractures: Good outcome in 13 patients

Strut allografts are not recommended after a femoral shaft exposure, because they may endanger the femoral blood supply. Up till now, we have seen no clinical reports on this problem. We treated 13 consecutive patients with very large anteromedial and anterolateral femoral strut allografts to restabilize periprosthetic fractures which had become loose after a previous attempt at surgical fixation (Vancouver type B fractures with severe bone loss). In 8 cases, the stem was revised in conjunction with the use of strut allografts and in 5 cases, strut allografts alone were used. All refractures and nonunions healed without further treatment. At a mean follow-up of 3 (1.2-7) years, the mean Harris Hip Score was 78 (65-92). All strut grafts showed ingrowth with augmentation of periprosthetic bone on the radiographs. There were 3 complications, 1 nonprogressive subsidence of a revision stem (fibrous stable), 1 deep hematoma and 1 partial lesion of the sciatic nerve. In this series, strut grafts gave reliable healing with augmentation of the host bone stock despite previous femoral exposure, severe bone loss, adverse type of fracture, and persistent instability at the index operation.     

Automated Assessment of Exclusion Criteria for DXA Lumbar Spine Scans

Modern bone densitometry systems using dual-energy X-ray absorptiometry (DXA) automatically analyze lumbar spine scans and provide clinically important information concerning spine bone mineral density (BMD) and fracture risk. Lumbar spine BMD accurately reflects skeletal health and fracture risk in most cases, but degenerative diseases associated with aging may lead to the formation of reactive bone (osteophytes) and other confounding conditions that elevate BMD without a concomitant increase in bone strength or decrease in fracture risk. Automated densitometry software known as computer-aided densitometry (CAD) (GE Medical Systems Lunar) assists the user in identifying scans with common acquisition and analysis irregularities known to influence BMD values. Visual examination of 231 female spine scans measured with DXA found abnormal conditions that could influence BMD results in 29% of scans. The sensitivity and specificity of several criteria for identifying scans with conditions that could influence BMD were determined. A good criterion for identifying scans with abnormal conditions was a T-score difference of greater than 0.9 or 1.0 between L1-L4 mean and individual vertebrae. Criteria for excluding affected vertebrae were determined. Exclusion of affected vertebrae resulted in a mean BMD decrease of nearly 0.6 SD (T-score) among affected scans.     

Periprosthetic fractures with extensive bone loss treated with onlay strut allografts

We reviewed a consecutive series of 19 patients with comminuted periprosthetic fractures, loosening of the femoral stem (Vancouver type B3) and significant loss of bone stock (Paprosky type III and IV). Sixteen porous-coated long stems and three Exeter stems, all with impaction grafting, were used. Large femoral onlay strut allografts were applied to maintain fracture reduction and improve stability. There was one early re-fracture at the tip of the femoral stem. Eighteen fractures healed without deformity and shortening. At the last follow-up at mean 3.7 (2.0-7.5) years, the mean Harris hip score was 76.4 (57.5-92.0). There was ingrowth of all strut grafts and significant augmentation of periprosthetic bone.     

Postoperative assessment of vascularity of the femoral head after surgical hip dislocation

Treatment for femoroacetabular impingement includes surgical hip dislocation and recontouring the femoral head-neck junction. However, a potential complication of this procedure is avascular necrosis. The purpose of this study was to assess radiographically the vascularity of the femoral head after surgical hip dislocation. Ten patients underwent surgical hip dislocation and recontouring of the femoral head-neck junction for femoroacetabular impingement. Postoperatively, all 10 patients underwent magnetic resonance imaging of the hip. Magnetic resonance imaging revealed no evidence of osteonecrosis in all patients. This study provides clear radiographic evidence that surgical hip dislocation may be performed without causing avascular necrosis of the femoral head.     

Pancreas after living donor kidney transplants in diabetic patients: impact on long-term kidney graft function

Abstract:  In this single-institution study, we compared outcomes in diabetic recipients of living donor (LD) kidney transplants that did vs. did not undergo a subsequent pancreas transplant. Of 307 diabetic recipients who underwent LD kidney transplants from January 1, 1995, through December 31, 2003, a total of 175 underwent a subsequent pancreas after kidney (PAK) transplant; 75 were deemed eligible (E) for, but did not receive (for personal or financial reasons), a PAK, and thus had a kidney transplant alone (KTA); and 57 deemed ineligible (I) for a PAK because of comorbidity also had just a KTA. We analyzed the three groups (PAK, KTA-E, KTA-I) for differences in patient characteristics, glycemic control, renal function, patient and kidney graft survival rates, and causes of death. Kidney graft survival rates (actuarial) were similar in the PAK vs. KTA-E groups at one, five, and 10 yr post-transplant: 98%, 82%, and 67% (PAK) vs. 100%, 84%, and 62% (KTA-E) (p = 0.9). The long-term (greater than four yr post-transplant) estimated glomerular filtration rate (GFR) was higher in the PAK than in the KTA-E group: 53 ± 20 mL/min (PAK) vs. 43 ± 16 mL/min (KTA-E) (p = 0.016). The patient survival rates were also similar for the PAK and KTA-E groups. We conclude that the subsequent transplant of a pancreas after an LD kidney transplant does not adversely affect patient or kidney graft survival rates; in fact, it is associated with better long-term kidney graft function.     

Indomethacin,ibuprofen and gentamicin administered during late stages of glomerulogenesis do not reduce glomerular number at 14 days of age in the neonatal rat

Premature neonates are frequently administered indomethacin, ibuprofen and gentamicin during the period of active glomerulogenesis. These drugs are known to have nephrotoxic effects, but the morphological effect of these drugs is unknown. The purpose of this study was to determine whether administration of these drugs during the late stages of glomerulogenesis in the rat has an effect on glomerular endowment. Rat pups were given, intraperitoneally, indomethacin, ibuprofen or indomethacin and gentamicin for the first 5 days of their postnatal life. The pups were killed at 14 days of age at completion of glomerulogenesis. The total number of glomeruli in the left kidney was determined by the physical disector/fractionator stereological technique. There was no difference between treatment groups in total number of glomeruli per kidney (P = 0.45). There were significantly fewer glomeruli per gram of kidney in those rat pups that had received indomethacin or ibuprofen (P < 0.0001). The reduction in the number of glomeruli per gram of kidney may indicate augmented growth of nephron tubules and/or collecting ducts, and/or be a consequence of oedema secondary to drug exposure. Further study is required to determine whether reduced glomerular number is seen in older animals or following exposure to these drugs at different time-points in kidney development.     

Femoral vein occlusion and spontaneous collateral ectasia presenting as recurrent hernia of the groin: a case report

Femoral vein occlusion is not a common complication even after repeated hernia repair. We describe a case of a 14-year-old boy with a visible and soft, yet irreducible, mass below the inguinal ligament after 3 previous inguinal hernia repairs and heart catheterization in infancy. Further examination showed dilated venous collaterals, bypassing an occluded common femoral vein via the testicular sheaths and across the pelvic floor. We discuss etiology, diagnostic pitfalls, therapeutic options, and possible future complications, with a literature review.