Prashanth Thakker

Understand how to accurately diagnose, manage, and treat acute kidney injury

Understand the etiology of chronic kidney disease and management of risk factors to reduce progression

Manage patients with end stage renal disease by learning about indications for dialysis and common complications in the patient population

Hypertension and electrolytes will be discussed at a later date**

An acute/abrupt worsening of renal function (<48 hours)

↑ Cr > 0.3mg/dl

↑ Cr >50% from baseline

UOP <0.5mL/kg/hr for >6 hours

History, history and more historyEvaluate the urine for sedimentFeNa or FeUrea

(Urine Sodium x Plasma Cr)/(Plasma Sodium x Urine Cr) (Urine urea x Plasma Cr)/(Plasma Urea x Urine Cr)

Renal UltrasoundSerologiesRenal Biopsy

History is key (volume, hemorrhage, ACE-I/ARB/NSAID, decreased effective circulatory volume – HF, cirrhosis)

BUN/Cr ratio of >20

Urine Osm > 500 osm/kg

FeNa <1%, FeUrea <35%

Stop agents which could worsen underling azotemia (will discuss exogenous agents)

Improve hemodynamics – if renal function improves then diagnostic and therapeutic

Systemic Hypotension and…

Usually associated with prior limited reserve or a co-existing insult (sepsis, drugs etc.) tubular and microvascular changes leading to tubular damage

More than just hemodynamically mediated…

Vascular changes in the setting of hemodynamic shift

Sepsis/Cytokine induced direct endothelial damage leading to microvascular thrombosis, ROS production etc. renal tubular injury

Rhabdomyolysis ATN History – traumatic crush injury, seizures, prolonged immobility

Lab findings – elevated myoglobin, CK, UA heme+, low RBC

Pathophysiology – renal vasoconstriction, direct tubular injury, and tubular obstr.

Treatment – fluids

*Hemolysis has a similar mechanism of action

TLS (Tumor Lysis Syndrome), Multiple myeloma

In TLS you have precipitation of Uric Acid causing tubular injury

Severe hypercalcemia can cause significant vasoconstriction and tubular damage

Myeloma proteins will precipitate and cause tubular obstruction

Antimicrobials Tubular necrosis – amphotericin B, aminoglycosides

AIN – PCN, cephalosporins, quinolones, sulfa, rifampin

Vancomycin w/ high troughs?

Tubular obstruction – acyclovir

Direct tubular damage – foscarnet, pentamidine, cidofivir

Contrast Induced Nephropathy ATN Serum creatinine rises in the first 24-48 hours, with peak 3-5 days and resolves in 1 week

Be weary with patient with underling renal disease!!

Pathophysiology involves direct tubular injury, hypoxia to the outer medulla due to occlusion of small vessels, transient tube obstruction

Fluids (pre-post), +/- bicarbonate

AIN Legionella Tubulointerstitial nephritis uveitis (TINU) syndrome

Acute Nephritic Syndromes (to be discussed)TTP/HUS

Recent GI disease, use of recent calcineurin inhibitors

Atheroembolic Recent vascular manipulation (usually large vessels)

Stop offending agents and treat underlying condition!!

Rhabdomyolysis – fluids

TLS – Allopurinol, Rasburicase

Volume overload – salt/water restriction, diurese, ultrafiltration

Hyperkalemia – decrease exogenous K+/meds ↑ K+, transient shift, and Kayexelate

Metabolic Acidosis – Bicarb if pH <7.2

Hyperphosphatemia – phosphate binders, phosphate restriction

DRUG DOSING

Classification of CKD1 (GFR > 90) – Treat underlying condition/comorbidities

2 (GFR 60 – 89) – Estimate Progression of disease3a (GFR 45-59) – Evaluate + treat complications3b (GFR 30-44) – Evaluate + treat complications4 (GFR 15-29) – Prepare for RRT5 (GFR <15) – HD if indicated

Diabetic Glomerular DiseaseGlomerulonephritisHypertensive Nephropathy

Primary glomerulopathy with HTN (FSGS) Vascular and ischemic renal disease

ADPKDOther cystic and tubulointerstitial kidney disease

1. Diabetic Nephropathy (55%)

2. Hypertensive nephropathy v Hypertension due to underlying vascular disease (33%)

3. Glomerulonephritis

4. Polycystic Kidney Disease

5. Obstructive Uropathy

Incidence – 40% patients with DM develop diabetic nephropathy

Progression usually seen in 5-10 years after DMI (seen as microalbuminuria), 30-300mg/g of albumin/creatinine ratio is considered microalbuminuria

Pathophysiology – increased glomerular pressures, glycosylation end products cause vascular disruption, filter barrier disruption, and glomerulosclerosis

Management – avoid progression through DM II control, blood pressure control (ACE-I/ARB to reduce intra-glomerular pressure)

Uncontrolled HTN can cause permanent damage in 6% of patients with uncontrolled HTN

Hypertension is the etiology for 27% of patients with ESRD Malignant hypertension in the setting of scleroderma and cocaine use can complicate the progression of hypertensive nephropathy

ACE-I and adequate blood pressure control is the way to go!

Nephritic v NephroticNephritic

Blood >> Protein 1-2g/day, pyuria, hematuria w/ casts, HTN, fluid retention

Nephrotic Protein >> Blood 3.5g/day (definition) for ‘nephrotic range’ proteinuria Nephrotic syndrome

ANCA + Vasculitis (Pauci-immune) – (40-45%) Wegener’s, Microscopic Polyangitis, Churg-Strauss

Immune Complex Disease (granular) – (40-45%) Post strep GN, MPGN, Fibrillary GN, IgA nephropathy SLE, Cryoglobinemia, Endocarditis, HSP

Anti-GBM (linear) - (15%)

FSGS (40%) Idiopathic, HIV, heroin, obesity

Membranous GN (30%) Idiopathic, HBV, HCV

Minimal Change Disease (20%) Idiopathic, NSAIDS

Membranoproliferative GN (5%) Infection (HCV, HBV), immune complex

Diabetic Nephropathy AL/AA Amyloid Light-chain deposition disease Lupus (WHO class V)

ADPKD occurs in 1:400–1:1000 individuals worldwide and accounts for ~4% of end-stage renal disease (ESRD) in the United States via the ADPKD-1 gene (85%)/ADPKD-2 gene

Hypertension precedes renal dysfunction

Associated complications include hepatic cysts, aortic root/annulus dilation, MVP, AI, Cerebral aneurysms

Treatment – HTN management, cyst/Pyelo should be treated with TMP/SMX or fluoroquinolones due to good cyst penetration

Potassium HemostasisMetabolic AcidosisDisorders of Calcium and Phosphate Ischemic Vascular DiseaseHeart failure, HTN, LVHAnemiaAbnormal Hemostasis

Calcium x Phos product

Calcium containing v non-calcium containing phos binders

Calcitriol

Osteitis fibrosa cystica

Usually starts off as livedo reticularis and then advances to patches of ischemic necrosis

Thought to be due to calcification of small-mid sized vessels leading to ischemia and necrosis

Associated with high Ca-Phos product > 55 Management includes local wound care, decrease Ca-Phos product

Reduction in erythropoietin leads to anemia usually in stage III or stage IV CKD

Managed by administration of erythropoietin in conjunction with iron, vitamin B 12, and folate to ensure adequate production by the marrow

Progression of CKD or AKI leading to any of the following:A – ACIDEMIAE – ELECTROLYTES (↑ K…↑P, ↑Mg, ↓Ca, ↓Na)I – INGESTION/TOXINSO – OVERLOAD (UF)U – UREMIA (pericarditis/encephalopathy)

Continuous Renal Replacement TherapyIntermittent HemodialysisContinuous Ambulatory Peritoneal DialysisContinuous Cyclic Peritoneal Dialysis

Hypotension Muscle Cramps Anaphylactoid Reaction to Dialysate

Type A (IgE-mediated intermediate hypersensitivity reaction) may need steroids and epi

Type B non-specific chest and back pain resolve over time

Continuous Ambulatory Peritoneal Dialysis Dialysis solution is manually infused into the peritoneal cavity and exchanged 3-5

times a day. Gravity is used to move fluid out of the abdomen

Continuous Cyclic Peritoneal Dialysis Dialysis solution is automatically cycled while the patient sleeps

Complications Peritonitis (WBC >100/mm3) Non-peritonitis infections Weight gain Hypoprotenimia

Etiology of ESRDRoute of dialysis (HD or PD) – mostly HDLocation and days of HD (last day of HD)AccessNephrologistDry WeightReview labs closelyReview medications and make sure renally dosed

FeverMissed Hemodialysis

DyspneaHyperkalemia

Vascular AccessChest Pain

Usually due to line infection, check all access sites! (other etiologies include HCAP, skin infection, C. dif) Cultures peripheral + HD line Review prior cultures including MIC (to see if they are building resistance)

Empiric Treatment Cover gram positives for line infection. Gram negatives are covered if there

patient is noted to be fairly ill. Vancomycin 20mg/kg load, followed by 10mg/kg post HD Zosyn 2,25q8h (HCAP), 2.25q12 otherwise Gentamicin is also an excellent choice given with HD

Volume overload Coordinate ultrafiltration with HD unit Make sure patient has access, if no access and HD stable can wait for IR to place

a line OR if there is concern for respiratory instability patient should go to MICU for temporary HD line placement (at this time it would be coordinated with renal MICU fellow)

Hyperkalemia Temporary measures include insulin/D50, Sodium Bicarbonate, Albuterol.

You can stabilize the cardiac membrane with calcium gluconate or chloride. Potassium binding agent in the GI tract kayexalate can be used

Keep you senior and renal fellow informed as patient may need HD sooner than you think!

Important to get history regarding last proper use. It is also important to examine the patient to look for thrill/bruit any signs of functionality of the graft or fistula

Contact Vascular Surgery if there is any concern for thrombosis and need for declottication

Again, urgent HD will always require the MICU

Mr. G is a 65 year old male with a past medical history of CHF presenting with worsening dyspnea on exertion and orthopnea. Patient notes a 30lb weight gain over the last month and significant lower extremity edema. He takes Lasix, Metoprolol Succinate, Lisinopril, Aspirin, and Spironolactone. Patient is afebrile, blood pressure of 140/90, heart rate 105. Patient is warm and wet with an elevated JVP and significant +3 lower extremity edema. His labs are consistent with a creatinine of 2.9 with a baseline of 1.2.

What do you want to do you think the etiology of the renal dysfunction is in this patient and what would your plan be?

Kasper DL, Harrison TR. Disorders of the Kidney and Urinary Tract. In: Harrison's Principles of Internal Medicine. New York: McGraw-Hill, Medical Pub. Division; 2005.

Armitage KB et al. Case Approach: A Resident Guide to Internal Medicine at UH Case Medical Center and the Cleveland VA 2016-2016. Cleveland: Case Medical Center; 2015.

Sabatine MS. Renal Failure. In: Pocket Medicine. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2011.