Prediction models using electronic clinical data accurately identified patients with elevated risk for hospitalization or death. This information can enhance the coordination of care for patients with complex clinical conditions.

Background Little is known about patterns of kidney function decline leading up to initiation of chronic dialysis. Study Design Retrospective cohort study. Setting and Participants 5,606 VA patients who initiated chronic dialysis in 2001–2003. Predictor: Trajectory of estimated glomerular filtration rate (eGFR) during the two year period before dialysis initiation. Outcomes and Measurements Patient characteristics and care practices before and at the time of dialysis initiation and survival after initiation. Results We identified four distinct trajectories of eGFR during the two year period before dialysis initiation: 62.8% of patients had persistently low levels of eGFR below 30 ml/min/1.73 m2 (mean eGFR slope 7.7 ±4.7 (SD) ml/min/1.73 m2 per year); 24.6% had progressive loss of eGFR from levels around 30–59 ml/min/1.73 m2 (mean eGFR slope 16.3 ±7.6 ml/min/1.73 m2 per year); 9.5% had accelerated loss of eGFR from levels above 60 ml/min/1.73 m2 (mean eGFR slope 32.3 ±13.4 ml/min/1.73 m2 per year); and 3.1% experienced catastrophic loss of eGFR within six months or less from levels above 60 ml/min/1.73 m2. Patients with steeper eGFR trajectories were more likely to have been hospitalized and to have an inpatient diagnosis of acute kidney injury. They were less likely to have received recommended pre-dialysis care and had a higher risk of death in the first year after dialysis initiation. Conclusions There is substantial heterogeneity in patterns of kidney function loss leading up to initiation of chronic dialysis, perhaps calling for a more flexible approach toward preparing for end-stage renal disease.

The bone morphogenetic proteins, BMP-2 and OP-1, are candidates for growth factors that control renal branching morphogenesis. We examined their effects in embryonic kidney explants and in the mIMCD-3 cell model of collecting duct morphogenesis (mIMCD-3 cells are derived from the terminal inner medullary collecting duct of the SV40 mouse). Osteogenic protein-1 (OP-1), at a dose of 0.25 nM, increased explant growth by 30% ( P = 0.001). In contrast, 100-fold greater concentrations of OP-1 (28 nM) decreased explant growth by 10% ( P < 0.001). BMP-2 was entirely inhibitory (maximum inhibition of 7% at 5 nM, P < 0.0004). In an in vitro model for branching morphogenesis utilizing the kidney epithelial cell line, mIMCD-3, low doses of OP-1 (<0.5 nM) increased the number of tubular structures formed by 28 ± 5% ( P = 0.01), whereas concentrations >0.5 nM decreased that number by 22 ± 8% ( P = 0.02). All concentrations of BMP-2 (0.05–10 nM) were inhibitory (maximum inhibition at 10 nM of 88 ± 3%, P < 0.0001). Stimulatory doses of OP-1 increased tubular length ( P = 0.003) and the number of branch points/structure (3.2-fold increase, P= 0.0005) compared with BMP-2. To determine the molecular basis for these effects, we demonstrated that BMP-2 is bound to mIMCD-3 cells by the type I serine/threonine kinase receptor, ALK-3, and that OP-1 bound to an ∼80-kDa protein using ligand-receptor affinity assays. To demonstrate that OP-1 can exert both stimulatory and inhibitory effects within a developing kidney, embryonic explants were treated with agarose beads saturated with 2 μM OP-1. OP-1 decreased the number of ureteric bud/collecting duct branches adjacent to the beads by 58 ± 1% ( P < 0.0001). In contrast, the number of branches in tissue distal to the OP-1 beads was enhanced, suggesting a stimulatory effect at lower doses of OP-1. We conclude that OP-1 and BMP-2 directly control branching morphogenesis and that the effects of OP-1 are dependent on its local concentration within developing kidney tissue.

Congenital anomalies of the kidneys and urinary tracts (CAKUT) are disorders caused by defects in the development of the kidneys and their outflow tracts. The formation of the kidneys begins at week 3 and nephrogenesis continues until week 36, therefore, the kidneys and outflow tracts are susceptible to environmental risk factors that perturb development throughout gestation. Many genes have been implicated in kidney and outflow tract development, and mutations have been identified in patients with CAKUT. In severe cases of CAKUT, when the kidneys do not form, the fetus will not survive. However, in less severe cases, the baby can survive with combined kidney and outflow tract defects or they may only be identified in adulthood. In this review, we will cover the clinical presentation of CAKUT, its epidemiology, and its long-term outcomes. We will then discuss risk factors for CAKUT, including genetic and environmental contributions. Although severe CAKUT is rare, low nephron number is a much more common disorder with its effect on kidney function increasingly apparent as a person ages. Low nephron number appears to arise by the same mechanisms as CAKUT, but it differs in terms of the magnitude of the insult and the timing of when it occurs during gestation. By understanding the causes of CAKUT and low nephron number, we can begin to identify preventive treatments and establish clinical guidelines for how these patients should be followed.