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Managing Glomerular Diseases

Fidel Barrantes M.D

Renal Medicine Associates

Presbyterian Transplant Center

University of Michigan

Objectives: Learn practical aspects on Glomerular disease

• Basic of Anatomy of physiology of the glomerulus

• Recognize the most common types of glomerulopathies

• When to refer to specialist

• Treatment

• Watching for treatment complications

Glomeruli : Anatomy and Histology

Pictures from www.uncnephropathology.com and www.siumed.edu

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Glomeruli: Anatomy of the filtration barrier

Physiology of Glomerular filtration

Pictures taken from www.studyblue.com

Physiology of mesangium and cell cross talk

Pictures taken from www.uncnephropathology.com and www.nature.com

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Diseases that affect glomeruli Immunologic

ANCA-Vasculitis Lupus Strep GN IgA Nephropathy

Non Immunologic Hypertension Obesity Obstruction

Primary Glomerular Minimal Change Disease Membranous GN FSGS Membranoproliferative C1q nephropathy IgA Nephropathy

Secondary Glomerular Diabetes Hypertension Obesity-FSGS Obstruction

Nephrotic Syndrome Minimal Change Disease Membranous GN FSGS Amyloidosis Diabetic Nephropathy Nephritic Syndrome Lupus Nephritis IgA Nephropathy ANCA vasculitis Anti-GBM

Autoimmune diseases and glomerular cells

Symptom Nephrotic Syndrome

Acute GN Rapid Progressively

GN

Asymptomatic proteinuria

and/or hematuria

Proteinuria >3.5 g/1.73 m2/per day

May be in nephrotic range

May be in nephrotic range

Not in nephrotic range

Hematuria Variable RBC casts and dysmorphic RBCs

RBC casts and dysmorphic RBCs

RBC casts and dysmorphic RBCs

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Symptom Nephrotic Syndrome

Acute GN Rapid Progressively

GN

Asymptomatic proteinuria

and/or hematuria

Blood Pressure

Normo- or hypertension

Hypertension Hypertension Normotension

GFR Variable decline, depending on diagnosis

Rapid decline (days to weeks)

Progressive decline (weeks to months)

Decline uncommon

When to refer to specialist:

• Nephrotic or Nephritic clinical features

• Significant edema with not clear explanation of liver or heart disease

• Rapid change in GFR

• Abnormal Urine sediment

• High blood pressure, especially with abnormal urine sediment

Minimal Change disease

Treatment Primary care focus

Steroids Cyclophosphamide (Rare) Cyclosporin (Relapses)

BP—ACEI, ARBs Volume- Diuretics Cholesterol Infection Prevention-Vaccine (flu, PNA, TB) Calcium and Vitamin D Watch out Steroids SE

•MCD is the most common cause of primary glomerular disease in children.

•The typical presentation is the nephrotic syndrome.

•Renal failure is uncommon, except in older adults.

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Focal Segmental Glomerulosclerosis

Treatment Primary care focus

Primary: Circulating Factor? Steroids Cyclosporin Secondary: Obesity, Obstruction, HIV, Heroine, Pamidronate Treat the cause

BP—ACEI, ARBs Volume- Diuretics Cholesterol Infection Prevention-Vaccine (flu, PNA, TB) Calcium and Vitamin D Watch out Steroids SE Weight loss, BP Management, Cholesterol

•FSGS is the most common cause of primary glomerular disease in African American adults.

•It typically manifest with the nephrotic syndrome.

•Patients are likely to present with an elevated creatinine level.

•It is the most common primary glomerular disease leading to ESRD.

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Membranous GN • MGN is one of the two most common primary glomerular diseases to cause nephrotic syndrome in adults.

• Severe proteinuria of more than 10 g/day and relatively normal serum creatinine level at presentation are not uncommon.

• Normal C3 and C4 levels are present,

Treatment Primary care focus

Primary: Observation Steroids Cyclosporin Secondary: Lupus or chronic hepatitis B, or paraneoplastic manifestation of extrarenal carcinomas Treat the cause

BP—ACEI, ARBs Volume- Diuretics Cholesterol Infection Prevention-Vaccine (flu, PNA, TB) Blood clots –DVT,PE Calcium and Vitamin D Watch out Steroids SE Treatment of underlying disease

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Ig A Nephropathy

Treatment Primary care focus

Primary:

Observation Steroids Cyclophosphamide Fish Oil

BP—ACEI, ARBs Volume- Diuretics Cholesterol Infection Prevention-Vaccine (flu, PNA, TB) Calcium and Vitamin D Watch out Steroids SE Gluten free diet

• Most common nephropathy world wide • It involves the temporal relation of hematuria to an upper respiratory tract infection. • Intermittent macroscopic hematuria, without proteinuria, and • persistent microscopic hematuria, with or without proteinuria, are the most common presentations.

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Crescentic GN: ANCA, ANTI GBM

Treatment Primary care focus

Steroids Cyclophosphamide Rituxan Plasmapheresis

BP Volume- Diuretics Cholesterol Infection Prevention-Vaccine (flu, PNA, TB) Calcium and Vitamin D Watch out Steroids SE Renal Prognosis may not be very good

Pictures taken from slideshares.net, pathologyatlas.ro

•Manifest with the nephritic syndrome as a renal-limited process or as part of a multisystem disease.

•Bimodal distribution, the first in the second to third decade of life and the second in the sixth and seventh decades. •Although serologic markers are specific (ANCA, MPO, PR3, anti-GBM) the delay in obtaining the results should not

postpone a kidney biopsy for a definitive diagnosis if clinical suspicion is high.

MPGN/C3 glomerulopathies •MPGN is more prevalent in children and young adults.

•The clinical presentation may be nephrotic syndrome, nephritic syndrome, or asymptomatic hematuria and

proteinuria.

•An active urine sediment and hypocomplementemia in the absence of systemic diseases are useful clinical clues.

Treatment Primary care focus

Depends of the etiology -Infection – Hepatitis C -Hematological malignancies -Complement problems -Lupus Steroids Cyclophosphamide Rituxan Plasmapheresis

BP Volume- Diuretics Cholesterol Infection Prevention-Vaccine (flu, PNA, TB) Calcium and Vitamin D Watch out Steroids SE Hep C treatment May need Hematological referral Renal Prognosis may be not very good

Pictures taken from www.uncnephropathology.com

LUPUS NEPHRITIS • Auto antibodies present- ANA, Anti Ds DNA, Anti Smith

• Nephritic or nephritic, depending Class

• Extra renal features present

Treatment Primary care focus

Depends of the Class Steroids Cellcept Cyclophosphamide Rituxan Plasmapheresis

BP Volume- Diuretics Cholesterol Infection Prevention-Vaccine (flu, PNA, TB) Calcium and Vitamin D Watch out Steroids SE Pregnancy precautions

www.unckidneycenter.org

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Immunoglobulin deposition diseases

Treatment Primary care focus

Depends of the Cause and Type Primary Malignancy Treatment Steroids Cyclophosphamide Rituxan Plasmapheresis

Hematological complications

• Single clone of plasma cell is responsible for over production of kappa or lambda chains • SPEP, UPEP, Serum free light chains, urine protein, UA

Graphic from www.medscpe.com

Myeloma Kidney

Treatment Primary care focus

Primary Malignancy Treatment : Melphalan, Bortezomib Steroids Plasmapheresis

Hematological complications Keep patient hydrates Watch and treat Hypercalcemia Limit diuretic use

Pictures from naturereviews.com, uncnephropathology.com

Diabetic Nephropathy

Pictures taken from www.theorganicdiabetes.org, www.diapedia.org, www.kidney-health.com, www.idneyfailureweb.com

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Diabetic Nephropathy

Graphics from Medscape.com and slidesshares.net

Slidesshares.net Kidney International 2014 86, 50-57DOI: (10.1038/ki.2014.98)

Diabetic Nephropathy Treatment Pathways

Nature Reviews Endocrinology 9, 713–723 (2013)

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Effect of the ACEI and ARB in DN-Trials Summary

Nature Reviews Nephrology 6, 371-380 (June 2010)

Hypertensive Nephropathy

Nature Reviews Nephrology 12, 27–36 (2016)

Hypertensive Kidney Histology

Nature Reviews Nephrology 12, 27–36 (2016)

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Better BP control in patients is better ( Target SBP <120mmhg)

Hypertensive Nephrosclerosis Effect of Calcium Antagonists

Kidney International 2004 65, 1991-2002DOI: (10.1111/j.1523-1755.2004.00620.x)

62 y with nephrotic syndrome and uncontrolled hypertension. GFR dropped from 45 to 25ml.min in 12 months

Rx Blood pressure control- ACEI, Diuretics Cholesterol Short steroids trial- developed SE Being prepared fro preemptive kidney transplant Latest GFR 20

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64 yo with worsening proteinuria (8g/24hrs) and hematuria Cr 1.9mg/dl

Rx -Steroids -BP control, ACEI -Diuretics -Weight control -Fish Oil Creatinine 1.0mgdl, Pr/cr 0.5

48 yo with worsening renal function, proteinuria

Rx -BP,volume control -DM Control -Weight loss -Listed preemptively for KT -Progressed to ESRD -Waiting for a KT

55 yo with Proteinuria and and decline in renal function

Rx -Pt lost to follow up -Started HD -Hematology f/u -No Malignancy

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45 Asian with edema, fatigue and cr 1.2mg/dl. Protein >300 in UA, microscopic hematuria

Rx. -Steroids and Cytoxan -BP: ACEI-cough> Losartan -Cholesterol -Creatinine 0.7, p/cr<0.3 -Doing very well

80 y very functionally active, with worsening renal function sent by NP to ER. Cr 0.7, 1 year before. Cr7 at presentation. Very mild hyper Ca and anemia.

Rx- -Bone Marrow Bx- MM -Rx of MM - 6 Months later died of MM complications

45 yo worsening kidney function after bacteremia, MSSA. Worsening renal function with abx (Nafcillin)

Rx -Abx changed to Cefazolin -Cr improved to 0.9 -Steroids short course -3 years later, Cr 0.8 ,no proteinuria -BP and weight control

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50 y with fatigue and tiredness and cough with blood sputum. Treated as PNA

Rx Steroids Cytoxan and PP BP and DM control 3 years later cr -0.7 mg/dl, normal Urine sediment

Conclusions • Be Alert when edema, dyspnea, Increased BP, hematuria, Fatigue, weight

loss/gain, appears

• Early referral to nephrologist

• Learn diagnosis and plan. Bx plan

• Control BP and Volume

• Watch and treat meds side effects

• Discuss with patients and nephrology renal prognosis

• Optimize Diabetes and Hypertension control

• Life style modifications

• Dose medication according to GFR

• Avoid further nephrotoxin medications-NSAIDs, Bactrim

• Don’t be afraid to use ACEI in proteinuric disease.