M1 Renal PBL - R2 Document PDF

# M1 Renal PBL - R2 Document ## Goal To use knowledge of normal body structure and function to investigate the case of a pregnant woman and integrate knowledge of blood pressure, kidney and electrolyte problems in her pregnancy. ## Case Resolution and Review The diagnosis for this patient is lup...

# M1 Renal PBL - R2 Document ## Goal To use knowledge of normal body structure and function to investigate the case of a pregnant woman and integrate knowledge of blood pressure, kidney and electrolyte problems in her pregnancy. ## Case Resolution and Review The diagnosis for this patient is lupus nephritis, class IV, a disease in which: * the glomeruli develop proliferative changes and crescent formation resulting from autoimmunity * leads to immune complex deposition in the glomerular capillaries * damage the tripartite glomerular capillary structure of endothelium, basement membrane and epithelium (podocytes) such that the permeability is altered, leading to proteinuria * the inflammatory response eventually results in a decrease in glomerular filtration surface area and a lower glomerular filtration rate (GFR) * treatment involves suppression of the immune system. Untreated, the process would lead to kidney failure and the need for dialysis. * in the peripartum period, the diagnosis of lupus nephritis often cannot be clearly distinguished clinically from preeclampsia which also causes high blood pressure and proteinuria in late pregnancy. ## Ms. Williams' Initial Visit On her initial visit, Ms. Williams presents with very subtle physical symptoms: * photosensitivity and joint pains. It is not uncommon for women in this age group to be on oral contraceptives and have iron deficiency anemia. * The photosensitivity could be attributed to "sunburn" but is in a specific distribution over the malar area. **The differential for such a rash includes systemic lupus erythematosus (SLE), from which the disease gets its name ("fox-like" rash) but the differential diagnosis includes other rashes with similar distribution (e.g., erysipelas, rosacea, pellagra (vit B3 deficiency), dermatomyositis, or even cellulitis).** Although it may be easy to dismiss the joint pains in the knees due to exercise, the pains in the wrist are less easy to attribute to running or jogging. Given her family history of maternal rheumatoid arthritis, an autoimmune disorder should be suspected. * **Her physical exam confirms the malar rash and the finding of effusions of the knees (excess fluid in the joint space).** Joint effusions can be caused by trauma, infection, crystals (gout), bleeding into the joint, damage to the cartilage or bone as well as autoimmune disease. Given the suspicion of autoimmune disease, her primary care physician appropriately orders a laboratory panel that shows: * she has a positive anti-nuclear antibody (ANA) but negative rheumatoid factor and normal complement. * She is anemic but her iron level is normal (saturation Fe/Iron binding capacity = 30%) suggesting another etiology, such as autoimmunity Together, she has four criteria for SLE: rash, joint involvement, positive ANA, and anemia. Importantly, she has normal renal function, urinalysis and glucose level. The advice her primary care doctor provided regarding prospectively getting pregnant is important as she is at high risk for complications during pregnancy and should be followed in a high-risk obstetrics clinic. ## Ms. Williams' Follow-Up Visit #1 Ms. Williams is ~ 12 weeks pregnant and feels well. Although plasma volume increases by 10-15% at this stage of pregnancy, plasma volume increases more than RBC volume, resulting in a small drop in hematocrit, which decreases blood viscosity and facilitates placental perfusion. Cardiac output increases but systemic vascular resistance decreases. Resting heart rate increases and blood pressure decreases modestly. Vasodilation is attributed primarily to a decrease in vascular responses to angiotensin II and norepinephrine and increased levels of nitric oxide. The increased levels of estrogen and progesterone also contribute to changes in vascular compliance during pregnancy. The immune system changes in a dynamic way during pregnancy. Among the immune changes, the increase in T regulatory cells (Tregs) at this stage of pregnancy helps maternal tolerance of the fetus and may also contribute to suppression of Ms. Williams' lupus symptoms until the peripartum period. The patient's creatinine has decreased indicating an increase in eGFR. This is the normal response to pregnancy. * The serum sodium is lower as the threshold for antidiuretic hormone is reset at a lower osmotic level. * Potassium declines as K is incorporated into the fetal cells. * Serum bicarbonate also drops as a result of mild hyperventilation (respiratory alkalosis). * The new presence of protein in the urine, albeit at a low level, is not normal and bears close monitoring. ## Ms. Williams' Follow-Up Visit at 36 weeks Gestation Near the end of her pregnancy, Ms. Williams develops headache and blurred vision with papilledema, swelling of the optic disc, all consistent with increased intracranial pressure. This is corroborated by the elevation in her blood pressure. These are serious symptoms and signs which may progress and lead to seizures if untreated. The edema around her eyes and worsening edema of her lower extremities indicates increased interstitial fluid due to changes in both serum oncotic pressure from low serum albumin and changes in capillary permeability. The low serum albumin is, in large part, due to losses as her urine protein has now increased to 4+. She also has RBCs in her urinalysis suggesting further damage to the kidney or urinary system. Notably her GFR has dropped substantially. **It is important to note that although the lab says eGFR > 60 ml/min/1.73m² is normal, it is her trajectory of renal function over the course of her case that is relevant.** Her bicarbonate has decreased beyond what would be expected for normal pregnancy thereby suggesting an inability of the kidney to excrete an acid load which needs to be evaluated further. Her hematocrit has also dropped along with the platelet count and her RBCs are fragmented (also called schistocytes) which indicates that the cells are breaking up, or hemolyzing. The two main potential diagnoses are preeclampsia or lupus flare with neural and renal involvement. She is treated with magnesium sulfate to decrease her blood pressure and prevent seizures. The mechanism is not fully known but data support that magnesium results in vasorelaxation and increases synthesis of nitric oxide as well as blocking receptors in the brain and altering neuromuscular transmission thereby preventing seizures. The treatment at this stage of pregnancy is to induce labor and she is given oxytocin, a hormone from the posterior. ## Ms. Williams' Postpartum Course Typically, delivery of the baby results in improvement in the case of preeclampsia. However, Ms. Williams' condition actually worsens with higher blood pressure, greater edema and worsening GFR. The immediate life threatening issue is her hyperkalemia which already shows changes in her ECG, namely peaked T-waves, due to shortening of phases 2 and 3 of the cardiac action potential (repolarization). The source of potassium is from the hemolyzed RBCs and inability of the patient to excrete the potassium due to declining renal function. The calcium gluconate increases the threshold potential, albuterol is a beta agonist and induces K to move intracellularly, and polystyrene sulfonate is a resin that binds K in the GI tract in exchange for Na causing increased excretion of K in the stool. Her acidosis which is now clearly metabolic with low pH, low bicarbonate, and low \(pCO_2\) (Find the point on the Davenport diagram). The urinalysis has also worsened with RBC and granular casts that are often seen with damage to the glomeruli. The quantitation of the urine protein shows that her protein loss is very high. Proteinuria \(\gt 3 mg/d\) is considered nephrotic and also indicative of injury resulting in increased permeability of the glomerular capillary barrier. The worsening of her serological markers indicate a lupus flare. Her renal biopsy shows crescent formation in Bowman's space and proliferation of cells in the glomeruli. Immunofluorescence is positive all along the glomerular basement membrane and electron microscopy shows deposits of immune complexes in both the subepithelial (below the podocytes) and subendothelial (below the endothelial cells) of the glomerular capillaries. The finding of all types of immunoglobulins and C3 in the immunofluorescence is typical of lupus nephritis. The proliferative and crescentic nature classify it as class IV which is a serious form of lupus nephritis. Without prompt treatment, the prognosis for renal failure and/or even death is high. She is advised not to breastfeed as the medications needed to treat her condition would be harmful to the infant. The use of an angiotensin converting enzyme inhibitor will bring down her blood pressure but also dilate her efferent arteriole thereby decreasing intraglomerular capillary pressure and diminishing proteinuria. Glucocorticoids are immunosuppressive. Cyclophosphamide inhibits the proliferation of T and B lymphocytes to antigen stimulation. Mycophenylate mofetil is an inhibitor of inosine monophosphate dehydrogenase preferentially in T and B lymphocytes, also inhibiting their proliferation and resulting in immunosuppression. Belimumab is a monoclonal antibody drug that binds to B-lymphocyte stimulator (also known as B cell activating factor) that promotes B cell survival and differentiation. Hydroxychloroquine was first used to treat malaria but is now used to inhibit pro-inflammatory cytokines. After 1 year of treatment, Ms. Williams renal function is better but not back to normal. She will need to be monitored closely.