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Case Report: PRaG 3.0 therapy for advanced cervical cancer with severe comorbidities
§Interactive anatomy

The Nephron Under Attack

Different agents injure different parts of the filtration unit. Walk the nephron from glomerulus to collecting duct, then localize injury with the biomarkers below.

Figure 1Mechanism in motion — cisplatin proximal tubulopathy
§Mechanism, step by step

How cisplatin injures the proximal tubule

The archetypal nephrotoxin traces a defined path: filtration, active transporter uptake, mitochondrial injury, and downstream electrolyte wasting. Scroll to follow the lesion from the S3 segment to the distal tubule.

How cisplatin injures the nephronA schematic nephron with a magnified proximal tubule epithelial cell. Filtered cisplatin is taken up across the basolateral membrane by OCT2 and organic anion transporters, injures S3 mitochondria to cause acute tubular necrosis, and downstream causes distal magnesium wasting.Mg²⁺Mg²⁺Mg²⁺OCT2OATPtPtGlomerulusProximaltubule (S1–S3)Loop of HenleDistal tubuleCollecting ductS3 epithelial cellBasolateral membraneLumen
Schematic · not to scale
Figure 2The nephron, segment by segment

Select any segment to see the agents documented to injure it and the mechanism at that site — from the glomerular filtration barrier through the proximal and distal tubule to the urothelium.

GlomerulusInterstitiumVasculatureProximal tubuleDistal / collecting ductTubular lumenBladder
select a segment to see what attacks it
Figure 3Injury burden across the nephron

Every profiled agent counted against the nephron segments each profile is documented to injure — the renal vasculature carries the heaviest load, the proximal tubule the next heaviest, and the bladder a distant last.

Injury burden by segment

Each site shaded in its own signature hue at an intensity scaled to the number of profiled agents documented to injure it. The renal vasculature and endothelium carry the largest count, ahead of the S1–S3 proximal tubule — whose apical and basolateral transporters (OCT2, OATs) concentrate nephrotoxic solute against the filtration gradient.

  • Vasculature / Endothelium
    Glomerular & peritubular capillaries
    182agents
  • Proximal Tubule
    Bulk reabsorption + drug uptake (OCT2, OATs)
    111agents
  • Glomerulus
    Filtration barrier (podocytes + endothelium)
    56agents
  • Distal Tubule / Collecting Duct
    Fine-tuning of Na, K, Mg, acid & water
    47agents
  • Tubular Lumen
    The urine flow path
    44agents
  • Interstitium
    Supporting tissue around the tubules
    38agents
  • Bladder / Urothelium
    Urine storage (outflow, not a nephron segment)
    3agents
FewerMore agents
481 segment-level injury assignments · peak 182
Figure 4From lesion to location — the injury-first view

The diagram above reads segment-first (pick a site, see its agents). This reads the other way: pick one of the 14 injury signatures to see where along the nephron it localizes and which agents carry it — the anatomical fingerprint of each lesion.

Injury signature

Localizes to

Glomerulus
Vasculature / Endothelium
Proximal Tubule

Bulk reabsorption + drug uptake (OCT2, OATs)

Distal Tubule / Collecting Duct

Fine-tuning of Na, K, Mg, acid & water

Interstitium
Tubular Lumen
Bladder / Urothelium

Agents causing ATN (75)

AfatinibAlpelisibArsenic trioxideAvutometinibAzacitidineBinimetinibBlinatumomabBRAF / MEK inhibitors (vemurafenib · dabrafenib · trametinib)CAR-T cell therapyCarboplatinCarfilzomibCiltacabtagene autoleucelCisplatinClofarabineCobimetinibDabrafenibDatopotamab deruxtecan (Dato-DXd)ElranatamabEnasidenibEncorafenibEnfortumab vedotinErlotinibFotemustineGallium nitrateIbandronateIbrutinibIdecabtagene vicleucelIfosfamideImatinibIobenguane I-131IvosidenibLenalidomideLifileucelLisocabtagene maraleucelLurbinectedinMelphalan flufenamide (melflufen)Methotrexate (high-dose)MobocertinibmTOR inhibitors (everolimus · temsirolimus)NedaplatinNimustine (ACNU)NivolumabObinutuzumabOdronextamabOxaliplatinPacritinibPegaspargasePemetrexedPenpulimabPentostatinPivekimab sunirinePlicamycin (mithramycin)PralatrexateProcarbazineRaltitrexedRituximabSacituzumab govitecanSamarium-153 lexidronamSirolimusSonidegibSotorasibStreptozocinSugemalimabTagraxofuspTalquetamabTarlatamabTasonerminTeclistamabTelisotuzumab vedotin (Teliso-V)TrabectedinTrastuzumab deruxtecanTretinoin (ATRA)VemurafenibVenetoclaxZoledronic acid
Which class strikes which segment →The same burden resolved by drug class — the class-family × nephron-segment heatmap lives on the Insights hub, alongside the rest of the data-viz.
§Reading the damage

Biomarkers that localize the injury

Creatinine rises late and lies often. These markers report on filtration, structure and segment-level function — not just whether the kidney is injured, but where.

Serum creatinine

Filtration (late marker)

Standard but insensitive — rises only after substantial GFR loss; confounded by muscle mass and cachexia.

eGFR

Estimated filtration

Used for CKD staging and chemotherapy dosing; unreliable in low-muscle, cachectic patients.

Cystatin C

Filtration, muscle-independent

Useful when creatinine misleads — sarcopenia, cachexia.

KIM-1

Proximal tubular injury

Rises early, before creatinine, in direct tubular damage.

NGAL

Early structural tubular injury

Detectable in urine and plasma hours before a creatinine bump.

Urine output

Real-time function

Part of the KDIGO/RIFLE criteria; oliguria flags AKI independently.

Electrolyte pattern

Tubular segment function

Magnesium wasting points distal; a full Fanconi picture points proximal.

Urine sediment

Injury localization

Granular casts (ATN), white cells (AIN), crystals (crystal nephropathy), schistocytes (TMA).

§Crystal nephropathy

Tumor Lysis Syndrome

Massive tumor-cell breakdown — spontaneous or triggered by treatment — floods the blood with uric acid, phosphate and potassium. Uric acid and calcium-phosphate crystals then precipitate inside the tubular lumen, obstructing flow and triggering AKI, usually 48–72 hours after therapy begins. Highest risk: bulky, fast-dividing, chemo-sensitive tumors such as Burkitt lymphoma, ALL and AML.

Howard et al., NEJM 2011 · PMID 21561350
The toxic triad
  • Uric acid. Precipitates in acidic tubular fluid → obstruction
  • Phosphate. Calcium-phosphate crystals deposit in the lumen
  • Potassium. Acute hyperkalemia — the lethal early threat