Polycystic kidney

disease
Dr Desi Salwani, SpPD-KGH
Polycystic kidney disease

• Inherited disease that involves bilateral kidney

cysts
• Autosomal dominant polycystic kidney disease
• Autosomal recessive polycystic kidney disease
ADPKD

• Most frequent genetic cause CKD for 6-10 % of

patients on dialysis
• Multisystemic and progressive disorder, cyst
formation & enlargement kidney, liver, pancreas,
spleen
• Clinical manifestations begin in 3-4 decade of life
• 50% require kidney replacement therapy by 60 years
of age.
ARPKD

• Cystic dilatation of kidney collecting ducts, along

with hepatic abnormalities of varying degrees,
including biliary dysgenesis and periportal fibrosis.

• The disorder is usually diagnosed in infants and

children, although hepatic involvement may not
manifest in neonates (50-60%).
Etiology

• Genetically heterogeneous involves 2 genes.

• PKD1 is located on chromosome 16p13.3 (>>>)
• PKD2 is located on chromosome 4q21-q22 (15%)

• Other genes : GANAB, ALG9, DNAJB11, and LRP5.

Pathophysiology

• systemic disease
• shows a focal expression; less than 1% of nephrons become
cystic.
• each epithelial cell within a renal tubule harbors a germ-line
mutation, yet only a tiny fraction of the tubules develop
kidney cysts.
• It is currently held that the cells are protected by the allele
inherited from the parent without ADPKD.
 Signs and symptoms
• Pain : abdomen, flank, or back
• Dull aching and an uncomfortable sensation of heaviness
• caused pain :
• Enlargement of one or more kidney cysts
• Bleeding: inside the cyst or lead to gross hematuria
with passage of clots or a perinephric hematoma
• Urinary tract infection : acute pyelonephritis, infected
cysts, perinephric abscess
• Nephrolithiasis and renal colic
• Hypernephroma
 Diagnosis
• Hypertension
• Palpable, bilateral flank masses, in advanced ADPKD
• Nodular hepatomegaly, in patients with severe polycystic
liver disease
• Rarely, symptoms related to advanced CKD ( pallor, uremic
fetor, dry skin, edema)
Testing

• Calcium and phosphorus

• Cell blood cell count
• Blood lipid
• Urinalysis
• Urine culture
• Uric acid
• Intact parathyroid hormone assay and vitamin D assay
• Genetic testing
 follows that of CKD
Staging of ADPKD
and is based on the estimated
glomerular filtration rate (GFR),
• Stage 1: GFR > 90 mL/min
• Stage 2: GFR 60-90 mL/min
• Stage 3: GFR 30-60 mL/min
• Stage 4: GFR 15-29 mL/min
• Stage 5: GFR < 15 mL/min
Imaging studies

• Ultrasonography: patients with ADPKD, screening patients'

family members; useful for exploring abdominal extrarenal
ADPKD (eg, liver cysts, pancreatic cysts)
• CT scanning: Not routine; complicated cases (eg, kidney
stone, suspected tumor)
• MRI: Not routine; renal cell carcinoma from simple cysts;
• Magnetic resonance angiography (MRA): Not routine;
intracranial aneurysms
Ravine et al, are very useful for identifying
patients at risk of pathogenic variants
in PKD1.
• The presence of fewer than 2 renal cysts has a negative
predictive value of 100% and can be considered sufficient to
exclude the disease in at-risk individuals over 40 years of
age.
• The diagnosis of ADPKD is established by any of the
following:
• At least 2 kidney cysts or 1 cyst in each kidney in patients younger than 30 years
• At least 2 cysts in each kidney in patients aged 30-59 years old.
• At least 4 cysts in each kidney in patients aged 60 years or older
Pei et al : USG criteria for ADPKD due to either PKD1 or PKD2 mutations
to screen patients with a family history of ADPKD but unknown
genotype :

• 3 atau > kidney cysts (unilateral or bilateral) in patients aged 15 to 39

years
• 2 or > cysts in each kidney in patients aged 40 to 59 years
• 4 or > cysts in each kidney in patients aged ≥60 years
• < 2 renal cysts in at-risk individuals aged ≥40 years excludes the disease
Indications MRA

• Family history of stroke, intracranial aneurysm (ICA), or hemorrhage; patients

with a family history of ICA and a negative
screening study should be rescreened at 5-10–year
intervals
• Before major elective surgery
• Central nervous system signs or symptoms (eg,
nausea and
vomiting, lethargy, photophobia, focal signs,
seizure, transient ischemic attack, loss of
consciousness)
• High-risk occupation or hobby,
in which a loss of consciousness
may be lethal (eg, airline pilot)
• New-onset severe headache

• Patient anxiety despite adequate information

 Management

• Control blood pressure

• Drugs of choice are ACEIs or ARBs

• Control abnormalities related to advanced CKD

• Drugs to maintain electrolyte levels (eg, calcium carbonate, calcium acetate, sevelamer, lanthanum
carbonate, calcitriol, diuretics)

• Treat kidney and liver cyst infections

• Gyrase inhibitors (eg, ciprofloxacin, ceftriaxone, clindamycin); dihydrofolic acid inhibitors
(TMX/SMP)

• Treat hematuria
• Copious oral hydration; consider analgesics

• Reduce abdominal pain caused by enlarged kidneys

• Prevent cardiac valve infection in patients with intrinsic valve disease
• Slow kidney function decline in adults at risk of rapidly progressive ADPKD
(tolvaptan)
 Surgical intervention in ADPKD

• Surgical drainage: Usually in conjunction with ultrasonography-

or CT-guided puncture; in cases of infected kidney/liver cysts not
responding to conventional antibiotics
• Open or fiberoptic-guided surgery: For excision/drainage of the
outer walls of cysts to relieve symptoms
• Nephrectomy: Last resort for control of pain or hematuria in patients
with inaccessible cysts in the renal medullae; bilateral
nephrectomy in patients with severe hepatic involvement
• Partial hepatectomy: To manage massive hepatomegaly
• Liver transplantation: In very rare cases of portal hypertension due
to polycystic liver or hepatomegaly with nonresectable areas
Patients with ADPKD who progress
to KRT
• Hemodialysis
• Peritoneal dialysis
• Kidney transplantation
Acute tubular
necrosis
Acute tubular necrosis

• Most common cause of AKI , leading to 3 possible mechanisms of injury to the

renal tubular epithelial cells:
• Afferent arteriolar vasoconstriction in response to tubuloglomerular
feedback
• Backleak of glomerular filtrate
• Tubular obstruction
• Well-defined 4-part
• Initiation
• Extension
• Maintenance
• Recovery
Acute tubular necrosis
• The initiation phase
• Characterized by an acute decrease in GFR, increase Cr and BUN

• The extension phase

• Characterized by ongoing hypoxia --- tissue ischemia --- inflammatory response.
• Limited blood supply, the corticomedullary junction of the kidney is most susceptible to a renal insult.
• A continuous release of cytokines and chemokines from impaired corticomedullary junction enhances
the inflammatory cascade—and this ongoing activation of the inflammatory cascade results in the
drop of GFR.

• The maintenance phase

• Characterized by a sustained reduction in GFR that persists for a variable length of time, most
commonly 1-2 weeks.
• Low GFR, the Cr and BUN levels continue to rise.
• Cellular repair from injury starts in this phase.

• The recovery phase

• Tubular function recover : increase in urine volume
• Decrease BUN and serum Cr
Etiology

• Ischemic-Induced Acute Tubular Necrosis

• Hypovolemic states
• Edematous states
• Sepsis or anaphylaxis
• Coagulopathy

• Nephrotoxic-Induced Acute Tubular Necrosis

• Causing direct proximal tubular injury, tubular obstruction, or renal vasoconstriction.
• Crystal-induced nephropathy due to high cell turnover such as uric acid, calcium phosphate
crystals in the setting of ongoing malignancy treatment.
• Light chain accumulation in multiple myeloma is directly toxic to the renal proximal and distal
tubules.

• Sepsis-Induced Acute Tubular Necrosis

• Systemic hypotension and renal hypoperfusion, endotoxemia leading to AKI by renal
vasoconstriction and the release of inflammatory cytokines causing enhanced secretion of
reactive oxygen species and leading to renal injury
Etiology

• Acute event, either ischemic or toxic.

• Sepsis in approximately 20% of ICU
• Prerenal azotemia, obstruction, glomerulonephritis,
vasculitis, acute interstitial nephritis, acute on chronic injury
(in patients with chronic kidney disease [CKD]), and
atheroembolic injury account for most of the remainder.
Causes of ischemic acute tubular
necrosis
• Hypovolemic states: Hemorrhage, volume depletion from GI or renal losses, burns,
fluid sequestration
• Low cardiac output states: Heart failure and other diseases of myocardium,
valvulopathy, arrhythmia, pericardial diseases, tamponade
• Systemic vasodilation: Sepsis, anaphylaxis
• DIC
• Surgical procedures in which renal blood flow is compromised (eg, those that involve
clamping of the renal artery, such as CABG, aortic dissection repair, renal cell
carcinoma resection)
• Causes of ischemic ATN vary depending on the studied population.
• In developed countries, comorbidities, older age, & severity of illness during ICU admission,
Comorbidities include cancer, hypertension, chronic heart failure, cirrhosis, AIDS, COPD, and DM.
• In low-income countries or rural areas : younger patients, volume depletion and complications of
pregnancy.
Causes of nephrotoxic acute
tubular necrosis
• The kidney is a particularly vulnerable target for toxins, both exogenous and endogenous. Not only
does it have a rich blood supply, receiving 25% of cardiac output, but it also helps in the excretion of
these toxins by glomerular filtration and tubular secretion.
• Exogenous nephrotoxins that cause ATN
• Aminoglycoside-related toxicity occurs in 10-30% of patients receiving aminoglycosides, even when blood levels
are in apparently therapeutic ranges. Risk factors for ATN in these patients include the following:
• Preexisting liver or kidney disease
• Concomitant use of other nephrotoxins (eg, amphotericin B, radiocontrast media, cisplatin)
• Shock
• Advanced age
• Female sex
• Higher aminoglycoside level 1 hour after dose (a high trough level has not been shown to be an independent risk
factor)
Exogenous nephrotoxins that can
cause ATN
• Cyclosporine and tacrolimus (calcineurin inhibitors)
• Cisplatin
• Ifosfamide
• Foscarnet

• Pentamidin to treat Pneumocystis jiroveci

• Sulfa drugs
• Acyclovir and indinavir
• Tenofovir
• Mammalian (mechanistic) target of rapamycin (mTOR) inhibitors (eg, everolimus,
temsirolimus
Endogenous nephrotoxins that
cause ATN
• Myoglobinuria
• rhabdomyolysis is the most common cause of heme pigment–associated AKI and
can result from traumatic or nontraumatic injuries. nontraumatic, such as related to
alcohol abuse or drug-induced muscle toxicity (eg, statins or fibrates).

• Hemoglobinuria
• associated with transfusion reactions (in contrast to myoglobin, hemoglobin has no
apparent direct tubular toxicity

• Acute crystal-induced nephropathy

• Multiple myeloma
• Renal impairment from accumulation and precipitation of light chains, which form
casts in the distal tubules that cause renal obstruction.
[29]
• Myeloma light chains have a direct toxic effect on proximal renal tubules.
Epidemiology

• The landmark PICARD (Program to Improve Care in Acute

Renal Disease) study was an observational study of a cohort
of 618 patients with AKI in the intensive care units of 5
academic centers in the United States.
• Ischemic ATN was the presumed etiology for 50% of all
patients with renal failure, an additional ~12% due to
unresolved pre-renal factors, and ~25% from nephrotoxic
ATN.
History and Physical
• History and physical examination give a lot of clues in identifying a person with prerenal disease and
acute tubular necrosis, which is caused by decreased renal perfusion.
• diarrhea, vomiting, sepsis, dehydration, or bleeding that leads to tissue hypoxia can indicate a
risk of acute tubular necrosis.
• Hospitalized patients with events such as hypotension, sepsis, intraoperative events, use of
nephrotoxic agents such as radiocontrast media
• Physical findings such as
• Tachycardia, dry mucous membrane, decreased skin turgor, and cool extremities are findings
that can be present in patients with volume depletion and hypotension.
• Fever and hypotension are common manifestations of sepsis.
• Muscle tenderness is present in the setting of rhabdomyolysis.
• Intraabdominal hypertension that causes abdominal distension due to abdominal
compartment syndrome also impedes renal perfusion and raises the concern for acute
tubular necrosis.
Evaluation
• Urinalysis (UA)
• In prerenal disease : normal or may contain hyaline casts.
• Acute tubular necrosis shows muddy brown casts or renal tubular epithelial cells secondary to the sloughing of
tubular cells into the lumen due to ischemia or toxic injury.

• Fractional excretion of sodium (FENa)

• This is a good test to differentiate between acute tubular necrosis and prerenal disease,
• Value < 1% favoring prerenal disease & > 2% acute tubular necrosis.

• Urine sodium concentration

• Kidneys try to conserve sodium or lose sodium due to tubular injury with
• Values > 40 to 50 mEq/L indicating acute tubular necrosis and
• Value < 20 mEq/L suggestive of prerenal disease.

• Novel Biomarkers
• Serum cystatin C
• Urinary alpha one macroglobulin
• Beta-2 microglobulin, urinary liver-type fatty acid-binding protein (L-FABP), and kidney injury molecule 1 (KIM-1)
for the detection of proximal tubular damage, urinary interleukin-18 (IL-18) is known to differentiate ATN from
CKD, neutrophil gelatinase-associated lipocalin (NGAL)
 Prognosis
• Hospital survival rate 50%, 30% surviving for one year.
• Critically ill patients with severe AKI have higher mortality in the first 2 months
and less during long-term follow-up.
• Factors associated with an increased mortality rate
• Poor nutritional status
• Male sex
• Oliguria
• Need for mechanical ventilation
• Acute myocardial infarction
• Stroke
• Seizures
• Prognosis
Treatment / Management

• High-risk procedures and conditions:

• Cardiogenic shock
• Hemorrhagic shock
• Pancreatitis
• Severe burns
• Sepsis
• Hypovolemia
• Major surgery (cardiac bypass, vascular surgery such as abdominal
aortic aneurysm peripheral limb surgery, hepatobiliary surgery,
emergent surgical exploration)
 Treatment / Management
• Prevention of hypovolemia or hypotension, including
• Cessation of ACEI o AIRB in patients with low BP
• Optimization of volume status via IV fluids, to ensure adequate renal perfusion.
• Avoid Nephrotoxic medications including NSAIDs, antibiotics such as amphotericin B,
aminoglycosides, vancomycin, piperacillin/tazobactam, and radiocontrast agents.

• Diuretics : manage the volume status. Dopamine, fenoldopam, and atrial natriuretic peptide do not
provide any survival benefit in patients with acute tubular necrosis.

• Renal replacement therapy (RRT)

• Volume overload refractory to diuretics
• Hyperkalemia
• Signs of uremia
• Metabolic acidosis
Differential diagnose

• Acute kidney injury

• Acute glomerulonephritis
• Azotemia
• Tubulointerstitial nephritis
• Chronic kidney disease
• Drug-induced nephrotoxicity
Prognosis

• Mortality rate 60-70% with patients in a surgical

setting.

• Severe hypotension or acute respiratory distress

syndrome, the mortality rate ranges from 50% to
80%.

• Oliguric ATN have a worse prognosis

Complications

• Same as related to AKI

• Acid-base
• Electrolyte disturbances such as hypocalcemia, hyperkalemia related
to metabolic acidosis, and hyperphosphatemia.
• Volume overload is related to anuria or oliguria.
• Uremic complications lead to pericarditis, bleeding diathesis, and
altered mental status.
Pielonefritis akut
Dr. Desi Salwani, SpPD-KGH
 Pendahuluan
• Masalah yang sering terjadi pada semua usia terutama
pada perempuan.
• Hampir 50% perempuan pernah mengalami satu
episode ISK
• Sepertiga diantaranya terjadi pada usia 24 tahun.
 ETIOLOGI

• Sekitar 70-95% penyebab ISK adalah bakteri Escherichia coli.

• Bakteri lain yang juga sering menyebabkan ISK adalah

• Staphylococcus sp.,
• Pseudomonas aeruginosa,
• Klebsiella spp
• Acinetobacter spp dan
• Enterobacter spp.
 FAKTOR RISIKO

• Riwayat ISK sebelumnya • Pemasangan kateter dalam

waktu lama
• Post menopause
• Kebiasaan menahan kemih
• Hubungan seksual
• Konstipasi, terutama pada anak
• Leukorea
• Penyakit ginjal
• Diabetes mellitus
• Riwayat ditemukan kelainan
• Hiperplasia kelenjar prostat ginjal saat ibu hamil
• Striktur uretra • Kehamilan
• Batu saluran kemih • Anomali struktur saluran kemih
DIAGNOSIS KLINIS

• Pielonefritis non-komplikata akut

• Presentasi klini: Demam, menggigil, nyeri pinggang,
diagnosis lainnya dieksklusikan, tidak ada riwayat atau
bukti klinis kelainan urologis (USG, radiografi)
• Laboratorium:
≥10 leukosit/mm3, ≥104 CFU/ml*
 PENEGAKAN DIAGNOSIS

PEMERIKSAAN PENUNJANG
Fasilitas kesehatan tingkat pertama

Keruh bahkan dapat disertai warna merah

• Urinalisis
(hematuria), leukosituria, nitrit dan bakteri positif

Fasilitas kesehatan tingkat lanjut

• Kultur urin (untuk

ISK berulang): uropatogen pada biakan
urin porsi tengah ≥105 CFU/ml.
• USG saluran kemih,
BNO untuk menyingkirkan obstruksi atau
batu saluran kemih
DIAGNOSIS BANDING

Pielonefritis akut non-komplikata perlu dibedakan dengan

• Pielonefritis komplikata menggunakan pemeriksaan
penunjang.
• Pielonefritis komplikata sering menyebabkan obstruksi dan
kemudian berisiko terjadinya urosepsis.
KRITERIA
RUJUKAN

• Jika
ditemukan
ISK
komplikata
• Jika gejala
menetap
setelah 2
mingg
MONITORING PENGOBATAN

• Resolusi gejala 2-4

minggu setelah
pengobatan
• Pada penggunaan
antibiotika yang
tepat, keluhan pada
sistitis berkurang
dalam 24 jam,
• sedangkan pada
pielonefritis
keluhan
berkurang pada
48-72 jam
PROGNOSIS

• Komplikasi pada umumnya baik terutama bila faktor

yang mempersulitnya dapat dihilangkan kecuali bila
higiene genital buruk maka akan muncul rekuren
ataupun kekambuhan.
PENCEGAHAN

• Edukasi untuk pencegahan primer ISK:

• Cukup konsumsi air putih (40 ml/KgBB/hari)
• Tidak menahan kencing terlalu lama
• Membersihkan daerah kemaluan dengan benar setelah buang air besar dan buang air
• kecil
• Menghindari penggunaan celana yang terlalu ketat
• Menjaga kebersihan daerah kemaluan dan sekitarnya
• Menggantikatetersecarateratur

• Edukasi untuk pencegahan sekunder ISK:

• Anjuran tidak berhubungan seksual saat pengobatan ISK
• Kepatuhan pengobatan
• Tanda-tanda komplikasi yang perlu diwaspadai dan waktu kontrol kembali
TERIMAKASIH