Renal transplant recipients have an increased risk of non-melanoma skin cancer (NMSC) compared to in the general population. Here, we show polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of NMSC in a general, nontransplant setting, can predict risk of, and time to posttransplant skin cancer. Genetic variants, reaching predefined P-value thresholds were chosen from published squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) nontransplant GWAS. Using these GWAS, BCC and SCC PRS were calculated for each sample across three European ancestry renal transplant cohorts (n = 889) and tested as predictors of case:control status and time to NMSC posttransplant. BCC PRS calculated at P-value threshold 1 × 10 was the most significant predictor of case:control status of NMSC posttransplant (OR = 1.61; adjusted P = .0022; AUC [full model adjusted for clinical predictors and PRS] = 0.81). SCC PRS at P-value threshold 1 × 10 was the most significant predictor of time to posttransplant NMSC (adjusted P = 9.39 × 10 ; HR = 1.41, concordance [full model] = 0.74). PRS of nontransplant NMSC is predictive of case:control status and time to NMSC posttransplant. These results are relevant to how genomics can risk stratify patients to help develop personalized treatment regimens.

Background Cutaneous squamous cell carcinoma (cSCC) occurs with higher frequency and recurrence rates, increased morbidity and mortality, and more aggressive metastasis in kidney and heart transplant recipients compared to the general population but all transplant recipients do not develop cSCC. In addition, the phenotypic expression of cSCC among transplant recipients can vary between mild disease to extensive recurrent metastatic disease. These clinically observed differences in occurrence and severity of cSCC among transplant recipients suggest the possibility that an underlying genetic component might modify risk. Methods We identified 88 white post-transplant cSCC cases (71 kidney and 17 heart) and 300 white post-transplant controls (265 kidney and 35 heart) using a DNA biobank linked with de-identified electronic medical records. Logistic regression was used to determine adjusted odds ratios (OR) for clinical characteristics and single nucleotide polymorphisms (SNP) associated with cSCC in both a candidate SNP and genome wide analysis. Results Age (OR 1.08 [1.05–1.11], p<0.001) and azathioprine exposure (OR 8.64 [3.92–19.03], p<0.001) were significantly associated while gender, smoking tobacco use, dialysis duration and immunosuppression duration were not. Ten candidate SNPs previously associated with non-melanoma skin cancer in the general population were significantly associated with cSCC in transplant recipients. Genome wide association analysis implicated SNPs in genes previously associated with malignancy, CSMD1 (OR 3.14 [1.90–5.20]) and CACNA1D (OR 2.67 [1.73–4.10]). Conclusions This study shows an association of increasing age and azathioprine exposure with cSCC and confirms a genetic contribution for cSCC development in kidney and heart transplant recipients.

The occurrence of post-exercise proteinuria was investigated in intact and splenectomized dogs after treadmill running and swimming and compared to control experiments. Albumin and lysozyme were measured by radial diffusion. Urinary protein was analyzed by SDS-polyacrylamide gel electrophoresis. Swimming in the splenectomized dogs increased the albumin excretion in the first 30 min after exercise from 0.03 to 0.22 mg X min-1 and the lysozyme excretion in the same period from 0.11 to 0.75 micrograms X min-1. Swimming in intact dogs caused smaller increase in the lysozyme and albumin excretions during the exercise period itself as well as in the albumin excretion in the first 30 min after exercise. Running had no effect on urinary albumin or lysozyme but increased the low molecular weight protein fraction in the splenectomized dogs. Plasma lactate concentrations were higher during swimming in the splenectomized dogs than in the intact dogs. Possible mechanisms of post-exercise proteinuria are discussed.

Kidney dialysis evolves as we learn more about the uremic condition. At its earliest versions the major transport process was diffusion, the spontaneous movement of particles down a concentration gradient, stimulated by thermal agitation, and affected by the collision of the particles with each other and with barriers such as dialysis membrane pore side walls. As dialysis was utilized to replace kidney function ultrafiltration (UF) was required, which could be generated by osmotic, oncotic, or hydrostatic pressures. Consequently, solvent drag effects of the UF led to an appreciation of the importance of convective transport and its advantageous property of increasing the removal of larger molecular sized (molecular weight + steric hindrance effects) species. Thus, modern dialysis generally utilizes both diffusive and convective transport and current devices and equipment allow for either process to occur independently or in combination. However, during convection solute is removed but concentrations in the retentate may not decrease unless substitution fluid is administered, a process called hemofiltration. Diffusion can occur without any UF. Appreciation of these extremes is important to the understanding of modern dialysis. Currently, dialysis cannot replace the endocrine or metabolic functions of the kidney so our discussion will be restricted to solute and fluid removal.

A rapid and severe increase in blood pressure resulting in new or progressive end-organ damage is defined as hypertensive emergency. Clinicians should effectively use the patient interview, physical examination, and additional testing to differentiate hypertensive emergency from nonemergent hypertension. Patients with evidence or high suspicion for end-organ damage should be expediently referred from the outpatient setting to a higher level of care. Knowledge of appropriate hypertensive emergency management and the ability to initiate this care in the clinic could help reduce patient morbidity in certain situations. Patients presenting with nonemergent hypertension can continue to be safely managed in the clinic.