Liver mesenchymal stem cells are superior inhibitors of NK cell functions through differences in their secretome compared to other mesenchymal stem cells.

Liver-resident mesenchymal stem cells (L-MSCs) are superior inhibitors of alloreactive T cell responses compared to their counterparts from bone marrow (BM-MSCs) or adipose tissue (A-MSCs), suggesting a role in liver's overall tolerogenic microenvironment. Whether L-MSCs also impact NK cell functions differently than other MSCs is not known. We generated and characterized L-MSCs, A-MSCs and BM-MSCs from human tissues. The mass spectrometry analysis demonstrated that L-MSC secretome is uniquely different than that of A-MSC/BM-MSC, with enriched protein sets involved in IFNγ responses and signaling. When co-cultured with primary human NK cells, L-MSCs but not other MSCs, decreased surface expression of activating receptors NKp44 and NKG2D. L-MSCs also decreased IFNγ secretion by IL-2-stimulated NK cells more effectively than other MSCs. Cytolytic function of NK cells were reduced significantly when co-cultured with L-MSCs, whereas A-MSCs or BM-MSCs did not have a major impact. Mechanistic studies showed that the L-MSC-mediated reduction in NK cell cytotoxicity is not through changes in secretion of the cytotoxic proteins Perforin, Granzyme A or B, but through increased production of HLA-C1 found in L-MSC secretome that inhibits NK cells by stimulating their inhibitory receptor KIRDL2/3. L-MSCs are more potent inhibitors of NK cell functions than A-MSC or BM-MSC. Combined with their T cell inhibitory features, these results suggest L-MSCs contribute to the tolerogenic liver microenvironment and liver-induced systemic tolerance often observed after liver transplantation.

A Descriptive Study of Late Intensive Care Unit Admissions After Adult Solitary Kidney Transplantation.

OBJECTIVE: Kidney transplant recipients are at lifetime risk of requiring high acuity care. In the current study, we aimed to assess the reasons for delayed (> 30 days) intensive care unit (ICU) admissions post-transplant and causes of ICU-related mortality. METHODS: This is a retrospective study of a cohort of adult kidney transplant patients from January 1, 2007, through December 31, 2016, who required ICU admission after 30 days of transplantation. The admissions were divided into 3 groups based on their timeline between transplantation and ICU admission: 1. group 1 from 30 days to 6 months, 2. group 2 between 6-24 months, and 3. group 3 after 2 years. All admissions were categorized according to the primary organ system involved. RESULTS: A total of 285 (group 1: 50, group 2: 89, group 3: 146) patients required 404 ICU admissions (group 1: 57, group 2: 108, group 3: 239). Overall, cardiovascular system-related admissions (29.9%, 18.5%, 15.9%), infections (19.3%, 25.9%, 27.2%), and respiratory-related admissions (12.3%, 8.3%, 8.8%) were main causes in all 3 groups. A total of 24 (8.4%) patients died in the ICU. Most of the deaths occurred in men (79.2%), infection-related admissions (45.8%), and individuals with a functioning allograft (66.7%). Infections (45.8%) were the main causes of ICU-related mortality. Median time from transplantation to death was 2.3 years (interquartile range: 1.2-4.6). CONCLUSION: Kidney transplant patients continue to be at risk of requiring high acuity care long after transplantation. Most of these admissions are related to cardiopulmonary system involvement or infections. Overall, infections were the leading cause of ICU-related mortality.

Simultaneous bilateral laparoscopic nephrectomy with kidney transplantation in patients with ESRD due to ADPKD: A single-center experience.

Patients with autosomal dominant polycystic disease (ADPKD) may require bilateral nephrectomy (BN) in addition to kidney transplantation (KT) for symptom control. This study aims to compare simultaneous BNKT to contemporaneous controls by reviewing our cohort of ADPKD patients who underwent KT from a living donor from January 2014 to October 2019. Symptomatic patients who underwent laparoscopic BNKT were compared to KT alone. Clinical differences related to undertaking bilateral nephrectomies showed increased total kidney volumes (P < .001). We assessed operative parameters, complications, and clinical outcomes. The complications were classified according to the Clavien-Dindo system. In 148 transplant recipients, 51 underwent BNKT, and 97 KT alone. There was no difference in baseline demographics. BNKT recipients had longer cold ischemia time, required more ICU care, increased blood transfusions and longer hospital stays. The kidney function was similar in the first year in both groups, with no difference in delayed graft function, readmissions or severe grade III and IV complications within 3 months after surgery. Laparoscopic BNKT is safe and feasible at the time of living donor KT. Although higher acuity care is needed with a longer initial hospital stay, there are comparable posttransplant patient and allograft outcomes.

Characteristics and Outcomes of Kidney Transplant Recipients Requiring High-Acuity Care After Transplant Surgery: A 10-Year Single-Center Study.

OBJECTIVE: To study the characteristics and outcomes of a cohort of kidney transplant recipients who required high-acuity care after transplant surgery. PATIENTS AND METHODS: All adult (aged ≥18 years) solitary kidney transplant recipients from January 1, 2007, through December 31, 2016, were screened and those who required high-acuity care within the same hospitalization were enrolled. Patient demographic and clinical data were collected from the departmental database and electronic DataMart. RESULTS: Of 1525 patients, 266 (17.4%) required high-acuity care after the kidney transplant operation: 166 (62.4%) directly from the operating room and 100 (37.6%) after an interval during the same hospitalization. Overall, 2 main indications were hypotension (n=87; 32.7%) and cardiac rhythm disturbances (n=83; 31.2%). Recipients in the direct admission group had higher medium body mass index (31.0 [interquartile range, 26.6-36.0] vs 28.0 [interquartile range, 24.3-32.4] kg/m2; P<.001) and were more likely to have undergone a concomitant procedure with the transplant surgery. Overall, in-hospital mortality was 1.9% (n=5). CONCLUSION: In contemporary practice, patients with higher body mass index are more likely to require high-acuity care immediately after kidney transplant surgery. The most common reasons are hypotension and cardiac rhythm disorders. The overall intensive care unit mortality rate of these patients is low. However, these patients are at risk for graft loss and death in the long term compared with patients who do not require intensive care unit care after transplant surgery.

Simultaneous Hand-assisted Laparoscopic Bilateral Native Nephrectomy and Kidney Transplantation for Patients With Large Polycystic Kidneys.

OBJECTIVE: To describe our technique of simultaneous hand-assisted laparoscopic bilateral native nephrectomy (BNN) and kidney transplantation (KT) in patients with autosomal dominant polycystic kidney disease and present our experience. MATERIALS AND METHODS: We retrospectively reviewed a cohort of adult ESRD patients with symptomatic autosomal dominant polycystic kidney disease who underwent a hand-assisted laparoscopic BNN at the time of KT. We reviewed patients' and donor characteristics, and perioperative and postoperative outcomes. RESULTS: A total of 52 patients underwent hand-assisted laparoscopic BNN at the time of KT from January 2014 to October 2019. The median age of the recipients was 53.4 years, 57.7% were males, and the median body mass index was 29.0 kg/m2. All but one received a kidney from a living donor and the majority (86.5%) were pre-emptive. One patient required a small bowel resection due to an intraoperative small bowel injury. There was no solid organ injury during the procedure. All patients showed immediate allograft function and a steady decline in serum creatinine. The median decline in the creatinine and hemoglobin on day 1 was 1.2 mg/dL (inter quartile range 0.6-2.3) and 2.2 g/dL (inter quartile range 1.4-3.0), respectively. CONCLUSION: Simultaneous hand-assisted laparoscopic bilateral nephrectomy with KT through a modified Gibson incision is feasible and safe in the hands of an experienced laparoscopic surgeon without compromising allograft function.

Phenotypic, Transcriptional, and Functional Analysis of Liver Mesenchymal Stromal Cells and Their Immunomodulatory Properties.

The liver is an immunologically active organ with a tolerogenic microenvironment at a quiescent state. The immunoregulatory properties of the liver appear to be retained after transplantation because liver allografts can reduce alloresponses against other organs that are simultaneously transplanted. Mechanisms of this phenomenon remain unknown. Given the known immunomodulatory properties of mesenchymal stromal cells (MSCs), we hypothesized that liver mesenchymal stromal cells (L-MSCs) are superior immunomodulators and contribute to liver-mediated tolerance. L-MSCs, generated from human liver allograft biopsies, were compared with adipose mesenchymal stromal cells (A-MSCs) and bone marrow mesenchymal stromal cells (BM-MSCs). Trilineage differentiation of L-MSCs was confirmed by immunohistochemistry. Comparative phenotypic analyses were done by flow cytometry and transcriptome analyses by RNA sequencing in unaltered cell cultures. The in vitro functional analyses were performed using alloreactive T cell proliferation assays. The transcriptome analysis showed that the L-MSCs are different than the A-MSCs and BM-MSCs, with significant enrichment of genes and gene sets associated with immunoregulation. Compared with the others, L-MSCs were found to express higher cell surface levels of several select immunomodulatory molecules. L-MSCs (versus A-MSCs/BM-MSCs) inhibited alloreactive T cell proliferation (22.7% versus 56.4%/58.7%, respectively; P < 0.05) and reduced the frequency of interferon ɤ-producing T cells better than other MSCs (52.8% versus 94.4%/155.4%; P < 0.05). The antiproliferative impact of L-MSCs was not dependent on cell-to-cell contact, could be reversed incompletely by blocking programmed death ligand 1, and required a higher concentration of the competitive inhibitor of indoleamine 2,3-dioxygenase for complete reversal. In conclusion, L-MSCs appear to be uniquely well-equipped immunomodulatory cells, and they are more potent than A-MSCs and BM-MSCs in that capacity, which suggests that they may contribute to liver-induced systemic tolerance.

Preoperative Factors Predicting Admission to the Intensive Care Unit After Kidney Transplantation.

OBJECTIVE: To identify preoperative factors predicting early admission (within 30 days) of adult kidney transplant recipients to the intensive care unit (ICU). PATIENTS AND METHODS: This is a single-center retrospective study of consecutive kidney transplant recipients between January 1, 2007, and December 31, 2016. Children (aged <18 years) and patients who underwent simultaneous multiorgan transplantation were excluded from the analysis. Associations between demographic, transplant-related, and comorbidity variables with ICU admission within 30 days of transplantation were analyzed using univariate and multivariate logistic regression models. RESULTS: Of the 1527 eligible patients, 305 (20%) required early ICU admission. In univariate analysis, older age, higher body mass index (BMI), previous transplantation, myocardial infarction, congestive heart failure, obstructive pulmonary disease, longer ischemia time, pretransplant dialysis, and transplantation from a deceased donor were associated with increased odds of ICU admission. After multivariate adjustment, every 10-year increase in recipient age (odds ratio [OR], 1.26; 95% CI, 1.12-1.42; P<.001), 5-unit increase in BMI (OR, 1.11; 95% CI, 1.00-1.22; P=.049), pretransplant dialysis (OR, 1.57; 95% CI, 1.19-2.08; P=.002), and deceased donor transplantation (OR, 1.82; 95% CI, 1.29-2.55; P<.001) were associated with the increased risk of ICU admission. Preemptive transplantation (OR, 0.64; 95% CI, 0.48-0.84; P=.002) and living donor kidney transplantation (OR, 0.55; 95% CI, 0.39-0.77; P<.001) were associated with lower odds of ICU admission after transplantation. CONCLUSION: Recipient age, BMI, and the need for pretransplant dialysis are associated with a higher risk of early ICU admission after kidney transplantation, whereas living donor kidney transplantation and preemptive transplantation decrease these odds. Early referral of patients with end-stage renal disease for preemptive transplantation and living donor kidney transplantation can significantly reduce transplant-related ICU admissions.

Revisiting the liver's role in transplant alloimmunity.

The transplanted liver can modulate the recipient immune system to induce tolerance after transplantation. This phenomenon was observed nearly five decades ago. Subsequently, the liver's role in multivisceral transplantation was recognized, as it has a protective role in preventing rejection of simultaneously transplanted solid organs such as kidney and heart. The liver has a unique architecture and is home to many cells involved in immunity and inflammation. After transplantation, these cells migrate from the liver into the recipient. Early studies identified chimerism as an important mechanism by which the liver modulates the human immune system. Recent studies on human T-cell subtypes, cytokine expression, and gene expression in the allograft have expanded our knowledge on the potential mechanisms underlying immunomodulation. In this article, we discuss the privileged state of liver transplantation compared to other solid organ transplantation, the liver allograft's role in multivisceral transplantation, various cells in the liver involved in immune responses, and the potential mechanisms underlying immunomodulation of host alloresponses.

Urine and serum fetuin-A levels in patients with urolithiasis.

INTRODUCTION: Fetuin-A is a glycoprotein secreted by liver and has been shown to inhibit extraosseous mineralization. Urolithiasis may be a manifestation in the urinary tract due to fetuin deficiency in urine. The objective of this study was to compare the 24-h urine and serum fetuin-A levels of patients with and without urolithiasis. METHODS: Serum and 24-h urine fetuin-A levels were measured in 41 patients with bilateral, multiple, or recurrent urinary tract calculi (Group A) and 41 matched controls with no calculi (Group B). Fetuin levels were measured by enzyme linked immunosorbent assay. Serum and urine fetuin-A levels in the two groups were compared. RESULTS: The median (range) 24-h urine fetuin-A value in Group A was 11.9 (1.12-221) mg/day and in Group B was 37.7 (1.28-125) mg/day. This difference was statistically significant (Mann-Whitney test, P = 0.0169). The median (range) serum fetuin-A in Group A was 0.67 (0.05-2.68) g/L and in Group B was 0.99 (0.01-5.5) g/L. The difference between serum values in the two arms was not statistically significant (Mann-Whitney test, P = 0.1817). However, the serum creatinine-adjusted mean log serum fetuin and urine fetuin were significantly different in the two arms (P = 0.003). The mean ± standard deviation (range) serum creatinine in Group A was 0.98 ± 0.25 (0.56-1.58) mg% and in Group B was 0.83 ± 0.16 (0.58-1.18) mg% (two sample t-test, P = 0.0031). CONCLUSIONS: Patients with urolithiasis have lower urine fetuin-A and creatinine-adjusted serum fetuin-A levels.

Nanobacteria in the pathogenesis of urolithiasis: Myth or reality?

Stone formation in the urinary tract is a common phenomenon with associated morbidity. The exact physicochemical factors responsible for stone formation are not clearly known. Over the past decade considerable interest has been generated in defining the role of nanobacteria in urinary stone formation. A review of the available literature has been carried out to give insights into their nature and outline their role in stone formation. The two aspects of nanobacteria that need to be considered include its biological nature and the other merely as mineralo-protein complexes. Though the current literature favors the concept of mineralo-protein particles, further research is needed to clearly define their nature. Whether living or nonliving, these apatite forming nanoparticles appear to play role in kidney stone formation.

Focused ultrasound guided relocation of kidney stones.

PURPOSE: Complete removal of all fragments is the goal of any intervention for urinary stones. This is more important in lower pole stones where gravity and spatial orientation of lower pole infundibulum may hinder spontaneous passage of fragments. Various adjuvant therapies (inversion, diuresis, percussion, oral citrate, etc.) are described to enhance stone-free rate but are not widely accepted. Focused ultrasound-guided relocation of fragments is a recently described technique aimed at improving results of intervention for stone disease. Purpose of this review is to discuss development of this technology and its potential clinical applications. MATERIALS AND METHODS: Pubmed search was made using key words "Focused ultrasound" and "kidney stone". All English language articles were reviewed by title. Relevant studies describing development and application of focused ultrasound in renal stones were selected for review. RESULTS: Focused ultrasound has proven its efficacy in successfully relocating up to 8 mm stone fragments in vitro and in pigs. Relocation is independent of stone composition. The latest model allows imaging and therapy with a single handheld probe facilitating its use by single operator. The acoustic energy delivered by the new prototype is even less than that used for extracorporeal shock wave lithotripsy. Therapeutic exposure has not caused thermal injury in pig kidneys. CONCLUSION: Focused ultrasound-guided relocation of stones is feasible. Though it is safe in application in pigs, technology is awaiting approval for clinical testing in human beings. This technology has many potential clinical applications in the management of stone disease.

Egg in a cup.

A case of medullary type papillary necrosis diagnosed on nephrostogram is presented showing characteristic egg-in-cup appearance.

Painful varicoceles: Role of varicocelectomy.

The incidence of varicocele in the general population is up to 15%. It is estimated that the prevalence of pain with varicoceles is around 2-10%. Till the year 2000, only two studies evaluated efficacy of varicocelectomy in painful varicoceles with conflicting results. Over the past decade many other studies have addressed this issue and reported on the treatment outcome and predictors of success. We critically appraised studies published from March 2000 to May 2013 evaluating surgical management in painful varicoceles to provide an evidence based review of effectiveness of varicocelectomy in relieving pain in patients with symptomatic painful varicoceles. The association between varicoceles and pain is not clearly established. Conservative treatment is warranted as the first line of treatment in men with painful clinical varicoceles. In carefully selected men with clinically palpable varicoceles and associated characteristic chronic dull ache, dragging or throbbing pain who do not respond to conservative therapy, varicocelectomy is warranted and is associated with approximately 80% success. However, surgical success does not always translate into resolution of pain and pain might persist even when no varicoceles are detected postoperatively.

A novel computer based stent registry to prevent retained stents: Will patient directed automated short message service and letter generator help?

OBJECTIVE: The objective of this study was to evaluate the feasibility of a computer based stent registry with patient directed automated information system to prevent retained double J stents. MATERIALS AND METHODS: A stent registry system was developed in collaboration with our Computerized Hospital Information Processing Service Department. This computer based stent registry with patient directed automated information system was integrated with the existing clinical work station. We reviewed the records retrospectively and assessed the feasibility of the system in reminding clinicians and patients regarding the stent and its date of removal. RESULTS: In a short run at our department, this new system appeared feasible, with patients promptly responding to the short message service and letter alerts. CONCLUSIONS: Computer based stent registry with patient directed automated information system is feasible in a clinical setting. A prospective study is needed for evaluation of its efficacy in preventing retained stents.

Bladder decompression for chronic urinary retention may lead to upper tract bleeding.

Haematuria following decompression of a distended bladder is a well known condition. The bleeding in such cases originates in the bladder and resolves spontaneously. We describe an elderly man who had bleeding from the kidney following decompression of the bladder. This resulted in an extensive search for an upper tract tumour as a cause for haematuria.

Laparoscopic Palanivelu-hydatid-system aided management of retrovesical hydatid cyst.

Hydatid cysts of the retrovesical region are rare. They are often adherent to the adjacent bowel and bladder, and complete removal is associated with potential injuries. The Palanivelu hydatid system allows minimally invasive treatment of hydatid cysts with no adjacent organ injuries. We describe the laparoscopic management of a pelvic hydatid cyst using this system.

Radiological seminal vesicle stones may actually be in the ureter.

Calculi in blind-ending ureters are uncommon. We describe a rare case of calculi in the diverticulum of a blind-ending ureter associated with ipsilateral renal agenesis, which masqueraded as seminal vesicle calculi.

Acute gastric dilatation: a rare complication of nephrectomy.

We report the first case of acute gastric dilatation after simple extraperitoneal nephrectomy for benign disease.