NP19 Nephrology

Parenchymal Kidney Diseases

3. THROMBOTIC MICROANGIOPATHY
etiologies include the spectrum of TTP-HUS, DIC, severe preeclampsia
renal involvement more common in HUS than TTP
renal involvement characterized by fibrin thrombi in glomerular capillary loops arterioles
treatment
depends on cause
supportive therapy
TTP-HUS: plasma exchange, corticosteroids (splenectomy and rituximab if refractory)
avoid platelet transfusions and ASA
4. CALCINEURIN INHIBITOR NEPHROPATHY
cyclosporine and tacrolimus
causes both acute reversible and chronic, largely irreversible nephrotoxicity
major cause of kidney failure in other solid organ transplants (e.g. heart)
acute: due to afferent and efferent glomerular capillary constriction leading to decreased GFR
(tubular vacuolization)
prerenal azotemia
treatment: calcium channel blockers or prostaglandin analogs, reduce dose of cyclosporine
or switch to another immunosuppressive drug
chronic: result of obliterative arteriolopathy causing interstitial nephritis and CKD (striped
fibrosis), less frequent now due to lower doses of calcineurin inhibitors

Glomerular Diseases
HISTOLOGICAL TERMS OF GLOMERULAR CHANGES
Extent of Changes
terms used to describe histologically the number of glomeruli affected in a given condition
diffuse: majority of glomeruli abnormal
focal: some glomeruli affected
terms used to describe histologically the extent to which individual glomeruli are affected in a
given condition
global: entire glomerulus abnormal
segmental: only part of the glomerulus abnormal
Types of Changes
proliferation: hyperplasia of one of the glomerular cell types (mesangial, endothelial, parietal
epithelial), with or without inflammatory cell infiltration
membranous changes: capillary wall thickening due to immune deposits or alterations in
basement membrane
crescent formation: parietal epithelial cell proliferation and mononuclear cell infiltration form
crescent-shape in Bowmans space
CLINICAL PRESENTATION OF GLOMERULAR DISEASE
Important Points to Remember
glomerular diseases have diverse clinical presentations including hematuria, proteinuria, HTN,
edema, and decreased GFR
each glomerulopathy presents as one of four major glomerular syndromes (these are NOT
diagnoses)
asymptomatic urinary abnormalities
proteinuria
hematuria
nephritic syndrome
acute GN
rapidly progressive GN
nephrotic syndrome
ESRD
glomerulopathies can be caused by a primary disease or can occur secondary to a systemic
disease
some glomerulopathies can present as more than one syndrome at different times
The Nephritic-Nephrotic Spectrum
glomerular pathology can present with a clinical picture anywhere on a spectrum with pure
nephritic and pure nephrotic syndromes at the extremes

Essential Med Notes 2015

Reduced Exposure to Calcineurin Inhibitors in

Renal Transplantation (ELITE-Symphony Trial)
NEJM 2007;257:2562-2575
Study: Multicenter, RCT with 12 mo follow-up.
Patients: 1,645 patients scheduled to receive a
single organ kidney transplant.
Intervention: Mycophenolate mofetil,
corticosteroids, and either: 1) standard dose
cyclosporine; 2) low dose cyclosporine with
daclizumab induction; 3) low dose tacrolimus with
daclizumab induction; 4) low dose sirolimus with
daclizumab induction.
Primary Outcome: Estimated Cockcroft-Gault GFR
12 mo after transplantation.
Results: The tacrolimus arm showed significantly
higher eGFR at 12 mo compared to all other arms
(65.4 mL/min vs. 57.1, 59.4, 56.7 for arms 1, 2,
4 respectively, p0.001). The tacrolimus arm
also showed decreased rates of acute rejection
at 6 mo and 12 mo vs. all arms (p<0.001),
improved allograft survival against standard
dose cyclosporine and sirolimus, and decreased
treatment failure against all other arms. There was
no difference in overall patient survival between
groups. Sirolimus had the highest incidence of
lymphoceles, delayed wound healing, and serious
adverse events; tacrolimus had significantly higher
rates of new-onset DM; and cyclosporine regimes
had the lowest incidence of diarrhea but highest
opportunistic infection rates.
Conclusion: Immunosuppression regiments using
low dose tacrolimus and daclizumab induction
decrease nephrotoxicity while maintaining
therapeutic immunosuppression in renal transplant
patients.