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Background: To analyze postoperative, in-hospital, complication rates in patients with organ transplantation before radical prostatectomy (RP). Methods: From National Inpatient Sample (NIS) database (2000–2015) prostate cancer patients treated with RP were abstracted and stratified according to prior organ transplant versus nontransplant. Multivariable logistic regression models predicted in-hospital complications. Results: Of all eligible 202,419 RP patients, 216 (0.1%) underwent RP after prior organ transplantation. Transplant RP patients exhibited higher proportions of Charlson comorbidity index ≥2 (13.0% vs. 3.0%), obesity (9.3% vs. 5.6%, both p < 0.05), versus to nontransplant RP. Of transplant RP patients, 96 underwent kidney (44.4%), 44 heart (20.4%), 40 liver (18.5%), 30 (13.9%) bone marrow, <11 lung (<5%), and <11 pancreatic (<5%) transplantation before RP. Within transplant RP patients, rates of lymph node dissection ranged from 37.5% (kidney transplant) to 60.0% (bone marrow transplant, p < 0.01) versus 51% in nontransplant patients. Regarding in-hospital complications, transplant patients more frequently exhibited, diabetic (31.5% vs. 11.6%, p < 0.001), major (7.9% vs. 2.9%) cardiac complications (3.2% vs. 1.2%, p = 0.01), and acute kidney failure (5.1% vs. 0.9%, p < 0.001), versus nontransplant RP. In multivariable logistic regression models, transplant RP patients were at higher risk of acute kidney failure (odds ratio [OR]: 4.83), diabetic (OR: 2.81), major (OR: 2.39), intraoperative (OR: 2.38), cardiac (OR: 2.16), transfusion (OR: 1.37), and overall complications (1.36, all p < 0.001). No in-hospital mortalities were recorded in transplant patients after RP. Conclusions: Of all transplants before RP, kidney ranks first. RP patients with prior transplantation have an increased risk of in-hospital complications. The highest risk, relative to nontransplant RP patients appears to acute kidney failure.
Sphingosine 1 phosphate (S1P) lyase (Sgpl1) catalyses the irreversible cleavage of S1P and thereby the last step of sphingolipid degradation. Loss of Sgpl1 in humans and mice leads to accumulation of sphingolipids and multiple organ injuries. Here, we addressed the role of hepatocyte Sgpl1 for regulation of sphingolipid homoeostasis by generating mice with hepatocyte-specific deletion of Sgpl1 (Sgpl1HepKO mice). Sgpl1HepKO mice had normal body weight, liver weight, liver structure and liver enzymes both at the age of 8 weeks and 8 months. S1P, sphingosine and ceramides, but not glucosylceramides or sphingomyelin, were elevated by ~1.5–2-fold in liver, and this phenotype did not progress with age. Several ceramides were elevated in plasma, while plasma S1P was normal. Interestingly, S1P and glucosylceramides, but not ceramides, were elevated in bile of Sgpl1HepKO mice. Furthermore, liver cholesterol was elevated, while LDL cholesterol decreased in 8-month-old mice. In agreement, the LDL receptor was upregulated, suggesting enhanced uptake of LDL cholesterol. Expression of peroxisome proliferator-activated receptor-γ, liver X receptor and fatty acid synthase was unaltered. These data show that mouse hepatocytes largely compensate the loss of Sgpl1 by secretion of accumulating sphingolipids in a specific manner into blood and bile, so that they can be excreted or degraded elsewhere.
Biological exploration of early biomarkers for chronic kidney disease (CKD) in (pre)diabetic individuals is crucial for personalized management of diabetes. Here, we evaluated two candidate biomarkers of incident CKD (sphingomyelin (SM) C18:1 and phosphatidylcholine diacyl (PC aa) C38:0) concerning kidney function in hyperglycemic participants of the Cooperative Health Research in the Region of Augsburg (KORA) cohort, and in two biofluids and six organs of leptin receptor-deficient (db/db) mice and wild type controls. Higher serum concentrations of SM C18:1 and PC aa C38:0 in hyperglycemic individuals were found to be associated with lower estimated glomerular filtration rate (eGFR) and higher odds of CKD. In db/db mice, both metabolites had a significantly lower concentration in urine and adipose tissue, but higher in the lungs. Additionally, db/db mice had significantly higher SM C18:1 levels in plasma and liver, and PC aa C38:0 in adrenal glands. This cross-sectional human study confirms that SM C18:1 and PC aa C38:0 associate with kidney dysfunction in pre(diabetic) individuals, and the animal study suggests a potential implication of liver, lungs, adrenal glands, and visceral fat in their systemic regulation. Our results support further validation of the two phospholipids as early biomarkers of renal disease in patients with (pre)diabetes.